Error checking and repair systems in the cell, amazing evidence of design

Otangelo · Last edited by Otangelo on Mon Oct 31, 2022 9:21 am; edited 107 times in total

A Second Round of Proofreading

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New Way That Cells Fix Damage To DNA Discovered

Repair through alkyltransferase-like proteins (ATLs)

DNA damage repair is a fascinating topic in cell biology. Fascinating because the cell's repair mechanisms are so incredible. What's more the mechanisms are coordinated in a sophisticated control network. As one researcher put it, "it’s almost as if cells have something akin to a computer program that becomes activated by DNA damage, and that program enables the cells to respond very quickly."

Now a new mechanism has been discovered which repairs DNA alkylation damage (the erroneous addition of carbon groups to DNA bases). The new mechanism links two previously known mechanisms. Here is how one science writer describes these two mechanisms:

The DNA repair process that removes such toxic "lesions" is known as base repair, and uses a protein called AGT (O6-alkylguanine DNA-alkytransferase) to remove the alkyl group before DNA replicates. The protein essentially sticks a chemical finger inside the DNA to flip the damaged [base] out from the DNA helix structure so that its adduct is exposed and can be transferred from the [base] to a part of its protein structure. The [base] is now repaired and can rejoin cytosine with three hydrogen bonds linking them.

AGT is believed to act alone, but there is another, unrelated repair process—nucleotide excision repair (NER)—that uses lots of proteins in its pathway. This repair occurs when bulky adducts stuck to bases distort the sleek shape of the DNA helix. Then a whole group of proteins come in and remove a patch of bases that includes the adduct, and DNA polymerase follows and fills in the patch while adding the correct base back.

The new mechanism uses alkyltransferase-like proteins (ATLs) which are similar to the AGT protein. Like AGT, ATL attacks the DNA base that has suffered alkylation damage. But the ATL protein distorts the DNA structure significantly, and thus triggers the nucleotide excision repair (NER) mechanism.

This sophisticated and coordinated repair sequence was found in all three domains of life (prokaryotes, eukaryotes and archaea). For evolutionists this forces the absurd conclusion that such a sophisticated DNA repair interaction evolved early on. Before there was so much as an amoeba, evolution had worked wonders. The earliest crude cells must not have been so crude after all. Evolution incredibly worked miracles in those heady days of early life. As the researchers write:

Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life.

This conclusion that complexity comes early is often forced on evolutionists, in spite of the evolutionary expectations to the contrary.

http://www.sciencedaily.com/releases/2009/06/090610133451.htm

A team of researchers at The Scripps Research Institute and other institutions has discovered a new way by which DNA repairs itself, a process that is critical to the protection of the genome, and integral to prevention of cancer development.

Scientists who study the repair of the DNA bases, which make up the information in the human genome, had known of only one type of method that cells use to fix a specific kind of damage to their DNA, but in the June 11, 2009 issue of Nature, the team found a novel way—one that combines elements from the known mechanisms and an unrelated second method that was previously not known to play a role in this type of DNA repair.

"We found a connection between the known DNA repair processes that people did not know was there," says Professor John Tainer, a member of the Skaggs Institute for Chemical Biology at Scripps Research, who led the study with Geoffrey P. Margison of the University of Manchester (United Kingdom) and Anthony E. Pegg of the Pennsylvania State University College of Medicine. "This changes the game, and gives us something important to look for in cancers that are resistant to chemotherapy."

This new mechanism is controlled by alkyltransferase-like proteins (ATLs), whose structure and function had been unknown and which had been identified only in bacteria and yeast. In addition to describing the function of ATLs, in the new study the scientists showed that ATLs exist in a multicellular organism, the sea anemone, which suggests this protein or its cousins in terms of repair activity also exist in other species, including humans.

Known Strategies for DNA Repair

Damage occurs to a cell's DNA on a continuing basis from outside sources, such as radiation and UV light, and from activities that go on day by day inside the cell. Most of this damage consists of damage to the DNA bases adenine, cytosine, guanine, and thymine. These bases pair up together inside the DNA double helix—adenine and thymine join together, and guanine and cytosine link to each other and their sequence forms the information in the human genome.

These bases can be chemically modified in a number of ways, including by alkylation, in which an alkyl group (or "adduct") is transferred onto a guanine base. When this happens, one of the hydrogen bonds holding guanine and cytosine together is removed, increasing the chances that thymine will be inserted across from guanine during DNA replication. If DNA is replicated with this "transition" error, a mutated gene results, so the information is changed. This can lead to harmful results, like cell death or cancer.

As shown in the reported work, this kind of damage occurs, for example, when chemicals derived from cigarette smoke stick to guanine, or when chemotherapy agents put an alkyl adduct onto guanine.

But that is where DNA repair mechanisms come in, which is good in the case of chemicals from cigarettes, but not so desirable when they repair genetic damage purposely induced by chemotherapy drugs intended to kill cancer cells.

The DNA repair process that removes such toxic "lesions" is known as base repair, and uses a protein called AGT (O6-alkylguanine DNA-alkytransferase) to remove the alkyl group before DNA replicates. The protein essentially sticks a chemical finger inside the DNA to flip the damaged guanine out from the DNA helix structure so that its adduct is exposed and can be transferred from the guanine to a part of its protein structure. The guanine is now repaired and can rejoin cytosine with three hydrogen bonds linking them.

AGT is believed to act alone, but there is another, unrelated repair process—nucleotide excision repair (NER)—that uses lots of proteins in its pathway. This repair occurs when bulky adducts stuck to bases distort the sleek shape of the DNA helix. Then a whole group of proteins come in and remove a patch of bases that includes the adduct, and DNA polymerase follows and fills in the patch while adding the correct base back.

A New Way

Before the new study, ATLs were believed to be involved in DNA damage responses, because they protected cells from DNA alkylation damage in lab experiments, but no one understood how they worked or what they did. In the new study, the team describes ATLs' role.

The scientists undertook a series of structural, genetic, and biochemistry experiments on the protein and determined its structure, both alone and with a guanine that had a methyl adduct and another with a smoking-derived adduct stuck on it. They found that the ATL structure looks like AGT. It, too, had a chemical finger that can rotate a damaged guanine base out from the DNA helix, but it doesn't remove the adduct like AGT does. Instead, ATL binds tightly to the damaged guanine and bends the DNA in a way that is more pronounced than what AGT does for repair.

"Base flipping by ATL is like a switch that activates the NER pathway, which then removes the alkyl adduct from the guanine," says first author Julie Tubbs, a research associate at Scripps Research. "So we believe that ATL is conceptually acting like a bridge, connecting the two DNA repair pathways—base and NER—together. This is a surprisingly general mechanism to channel specific base damage into the general NER pathway."

Before the new study, scientists also didn't know if ATLs functioned outside of single celled organisms. In the new study, however, the scientists discovered ATLs in two types of ancient organisms, archaeal bacteria and in sea anemone, suggesting this new bridging pathway may be general to most cells and organisms.

"What's especially important about these newly discovered ATLs is that we now know that ATLs exist in all domains of life, so it is very likely that ATL was common to the evolutionary branches before complex eukaryotes [single-celled or multicellular organisms whose cells contain a distinct membrane-bound nucleus]," Tainer says. "This suggests higher eukaryotes, including mammals and humans, will either have an ATL or have lost or replaced it with a protein of analogous function."

If ATLs are found in humans, Tainer sees that either inhibiting or bolstering their function could aid cancer therapy. Inhibiting DNA repair would help chemotherapy effectively destroy cancer cells. Augmenting ATL function could help protect sensitive tissue, such as bone marrow, that is easily destroyed during cancer treatment.

"There are all kinds of exciting ideas to emerge from this research," says Tainer. "For one thing, we now know what to look for when we see resistance to some chemotherapies."

In addition to Tainer, Margison, Pegg, and Tubbs, authors of the new study are Vitaly Latypov, Amna Butt, Andrew Marriott, Amanda J. Watson, Barbara Verbeek, Gail McGown, and Mary Thorncroft of the University of Manchester; Sreenivas Kanugula of the Pennsylvania State University College of Medicine; Manana Melikishvili and Michael G. Fried of the University of Kentucky; Rolf Kraehenbuehl and Oliver Fleck of Bangor University; Mauro F. Santibanez-Koref of the University of Newcastle-upon-Tyne; Christopher Millington and David M. Williams of the University of Sheffield; Lisa A. Peterson of the University of Minnesota; and Andrew S. Arvai and Matthew D. Kroeger of Scripps Research. Tainer also holds a position at Lawrence Berkeley National Laboratory.

The study was supported by the National Institutes of Health, The Skaggs Institute for Chemical Biology, U.S. Department of Energy, the North West Cancer Research Fund, Cancer Research-UK, and CHEMORES.

New Powerful DNA Repair Single Protein Complex Discovered 1

Normal but dangerous strand breaks occur with the DNA double helix about 10 times a day in every cell due to ultraviolet light and radiation damage, etc. This creates an emergency. If these breaks are not quickly repaired, serious chromosomal rearrangements can occur that lead to cancer. The first responder to rush to the rescue looks like an octopus, and wraps around the accident scene to perform the repairs. These mechanical technicians in the cell are now beginning to be understood after 10 years of research.

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Energy. A press release at the Scripps Research Institute states:

“In a paper published in an Advance Online Edition of Nature Structural and Molecular Biology March 27, 2011, the scientists say that the complex’s motor molecule, known as Rad50, is a surprisingly flexible protein that can change shape and even rotate depending on the task at hand.”

The research paper stated that the components of this super protein structure are “conserved,” which means unevolved. The report continues:

“The finding solves the long-standing mystery of how a single protein complex known as MRN (Mre11-Rad50-Nbs1) can repair DNA in a number of different, and tricky, ways that seem impossible for “standard issue” proteins to do, say team leaders Scripps Research Professor John Tainer, Ph.D., and Scripps Research Professor Paul Russell, Ph.D., who also collaborated with members of the Lawrence Berkeley National Laboratory on the study.”

The report further reads:

“The scientists say that the parts of the complex, when imagined together as a whole unit, resemble an octopus: the head consists of the repair machinery (the Rad50 motor and the Mre11 protein, which is an enzyme that can break bonds between nucleic acids) and the octopus arms are made up of Nbs1 which can grab the molecules needed to help the machinery mend the strands.”

When rescue workers initially arrive at an emergency scene, the first thing they must do is identify and assess the injuries. The report explains the general idea of the process:

“When MRN senses a break, it activates an alarm telling the cell to shut down division until repairs are made. Then, it binds to ATP (an energy source) and repairs DNA in three different ways, depending on whether two ends of strands need to be joined together or if DNA sequences need to be replicated.”

Tainer explains: “The same complex has to decide the extent of damage and be able to do multiple things. The mystery was how it can do it all.”

In this study, Tainer and Russell were able to produce crystal and X-ray scattering images of parts of where Rad50 and Mre11 touched each other. The four (4) images of what these proteins look like when the complex is bound to ATP and when it is not are displayed above.

The four images demonstrate how ATP binding allows Rad50 to drastically change its shape. When not bound to ATP, Rad50 is flexible and floppy, but bound to ATP, Rad50 snaps into a ring that presumably closes around DNA as if it were an octopus in order to repair it.

The research also reveals a busy transport system that Trainer refers to as “big movement on a molecular scale” involved with the repair operation. He added, “Rad50 is like a rope that can pull. It appears to be a dynamic system of communicating with other molecules.”

Aside from the complex cellular machinery involved in this process, the functions being performed are also quite sophisticated. This set of proteins has the ability to sense damage, then be transported substantial distances to the accident site to initiate repairs. The damage must be assessed, a choice must be made as to the correct procedure to restore the damage, and the proper materials must be retrieved to perform the repair work.

1) https://dennisdjones.wordpress.com/2011/03/28/new-powerful-dna-repair-single-protein-complex-discovered/

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Otangelo

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Special DNA polymerases are used in emergencies to repair DNA

If a cell's DNA is heavily damaged, the repair mechanisms are often insufficient to cope with it. In these cases, a different strategy is called into play, one that entails some risk to the cell. The highly accurate replicative DNA polymerases stall when they encounter damaged DNA, and in emergencies cells employ versatile but less accurate back-up polymerases to replicate through the DNA damage. Human cells contain more than l0 such DNA polymerases, some of which can recognize a specific type of DNA damage and specifically add the nucleotide required to restore the initial sequence. Others make only "good guesses," especially when the template base has been extensively damaged. These enzimes are not as accurate as the normal replicative polymerases when they copy a normal DNA sequence. For one thing, the backup polymerases lack exonucleolytic proofreading activity; in addition, many are much less discriminating than the replicative polymerase in choosing which nucleotide to initially incorporate. Presumably, for this reason, each such polymerase molecule is given a chance to add only one or a few nucleotides. Aithough the details of these fascinating reactions are still being worked out, they provide elegant testimony to the care with which organisms maintain the integrity of their DNA.

Its remarkable how the author chooses words which indicate design. Isnt it rather the creator who gave special care in order to provide integrity of the DNA ?

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Mismatch Repair (MMR) 1

DNA mismatch repair is a highly conserved pathway in which our cells repair base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Mismatch repair systems maintain the integrity of our genomes by suppressing non-homologous recombination and was recently shown to play a role in DNA damage signalling in eukaryotic cells. Defects in MMR increase the spontaneous mutation rate, and have been associated both hereditary and sporadic cancers.

The proteins unique to MMR were first identified in prokaryotes, in which the loss of such proteins resulted in increased mutations and a mutated phenotype. These proteins are known as the “Mut” proteins. Of all the “Mut” proteins, MutS, MutL, MutH are essential in detecting the mismatch and directing repair machinery to it.

Brief View of MMR Steps

The first step in the MMR system involves efficient recognition of helical distortions (mismatches) resulting from nucleotide misincorporation or DNA polymerase slippage. After that, the newly synthesized DNA strand containing the incorrect information must be selectively removed and re-synthesized. Strand discrimination is an essential feature of all MMR systems; in its absence, a replication error is just as likely to be used as a template for repair as it is to be repaired. Whereas the latter steps in MMR require proteins involved in general DNA metabolic processes, the initial mismatch recognition and removal steps require specialized Mut proteins, which are highly conserved evolutionarily.

1) http://warforscience.blogspot.com.br/2010/01/answering-creationist-claims-part-6-dna.html

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Molecular Machines Are Amazing Alone, but When They Cooperate -- Wow! 1

Our genomes are protected by multiple levels of monitoring and repair, so that most of us carry on from day to day, completely oblivious of the multiple information-guided processes in our cells that make life work. There are systems that can fix double-stranded breaks. There are systems that can replace incorrect DNA bases (letters) in the code. There are even machines that can push the panic button when errors are catastrophic, causing a damaged cell to shut down.

For science to comprehend these systems, it needs a framework fit for the information age. It needs familiarity with robotics and multi-level control. The biology of Charles Darwin's antiquated Victorian world, which imagined systems emerging from unguided processes, is hopelessly inadequate. Darwin did not foresee, and could not have fathomed, the technology at the basis of life.

A simple way to envision the action of UvrD in prokaryotes to promote RNA polymerase backtracking is the train engine analogy, in which a locomotive (RNA polymerase) encounters a railroad track buckle (DNA damage) and stalls. A second locomotive (UvrD in blue) is positioned at the rear end of the first locomotive, and the UvrD throttle is engaged to quickly and efficiently drag the stalled RNA polymerase locomotive away from the track buckle, so the repair crew can fix it. In this scenario, UvrD utilizes its force-producing ATP hydrolysis to haul the large 5-subunit RNA polymerase complex of ~400 kiloDalton backward, overcoming the driving force of the elongating RNA polymerase to translocate again toward the damage and obstruct the buckle. Once the lesion is repaired, RNA synthesis can resume. 2

Error checking and repair systems in the cell, amazing evidence of design Pubmed10

Error checking and repair systems in the cell, amazing evidence of design Pubmed10

2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049952/figure/F1/
1) http://www.evolutionnews.org/2014/01/molecular_machi_3081111.html

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As to; ‘DNA codes are far more sophisticated than their human counterparts, and they also have a variety of repair mechanisms.’

Repair mechanisms in DNA include:

A proofreading system that catches almost all errors
A mismatch repair system to back up the proofreading system
Photoreactivation (light repair)
Removal of methyl or ethyl groups by O6 – methylguanine methyltransferase
Base excision repair
Nucleotide excision repair
Double-strand DNA break repair
Recombination repair
Error-prone bypass

http://www.newgeology.us/presentation32.html

further note;

Quantum Dots Spotlight DNA-Repair Proteins in Motion – March 2010
Excerpt: “How this system works is an important unanswered question in this field,” he said. “It has to be able to identify very small mistakes in a 3-dimensional morass of gene strands. It’s akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.” Dr. Bennett Van Houten – of note: A bacterium has about 40 team members on its pothole crew. That allows its entire genome to be scanned for errors in 20 minutes, the typical doubling time.,, These smart machines can apparently also interact with other damage control teams if they cannot fix the problem on the spot.
http://www.sciencedaily.com/releases/2010/03/100311123522.htm

Moreover, “Quantum Information/Computation” which is not reducible to the materialistic framework of neo-Darwinism (A. Aspect), is found to be integral to DNA;

Quantum Information/Entanglement In DNA & Protein Folding – short video
http://www.metacafe.com/watch/5936605/

In the preceding video, ‘Gretchen’ asked if quantum entanglement/information could also somehow be measured in protein structures, besides just DNA, and it turns out that quantum entanglement/information has already been detected in protein structures. Here is one such measure;

Proteins with cruise control provide new perspective:
Excerpt: “A mathematical analysis of the experiments showed that the proteins themselves acted to correct any imbalance imposed on them through artificial mutations and restored the chain to working order.”
http://www.princeton.edu/main/news/archive/S22/60/95O56/

further notes;

3-D Structure Of Human Genome: Fractal Globule Architecture Packs Two Meters Of DNA Into Each Cell – Oct. 2009
Excerpt: the information density in the nucleus is trillions of times higher than on a computer chip — while avoiding the knots and tangles that might interfere with the cell’s ability to read its own genome. Moreover, the DNA can easily unfold and refold during gene activation, gene repression, and cell replication.
http://www.sciencedaily.com/releases/2009/10/091008142957.htm

DNA Optimized for Photostability
Excerpt: These nucleobases maximally absorb UV-radiation at the same wavelengths that are most effectively shielded by ozone. Moreover, the chemical structures of the nucleobases of DNA allow the UV-radiation to be efficiently radiated away after it has been absorbed, restricting the opportunity for damage.
http://www.reasons.org/dna-soaks-suns-rays

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living creatures must have elaborate DNA repair machinery. University of Chicago biologist James Shapiro points out that:

all cells from bacteria to man possess a truly astonishing array of repair systems which serve to remove accidental and stochastic sources of mutation. Multiple levels of proofreading mechanisms recognize and remove errors that inevitably occur during DNA replication. … cells protect themselves against precisely the kinds of accidental genetic change that, according to conventional theory, are the sources of evolutionary variability. By virtue of their proofreading and repair systems, living cells are not passive victims of the random forces of chemistry and physics. They devote large resources to suppressing random genetic variation and have the capacity to set the level of background localized mutability by adjusting the activity of their repair systems

Shapiro, J.A., A Third Way, Boston Review, p. 2, February/March 1997

http://creation.com/DNA-repair-enzyme#txtRef5

Otangelo · 8 DNA errors are scanned electrically Mon Jun 15, 2015 4:51 pm

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DNA errors are scanned electrically

https://reasonandscience.catsboard.com/t2043-dna-and-rna-error-checking-and-repair-amazing-evidence-of-design#3498

Electric DNA
Our cells have elaborate machinery to repair DNA. But with 3 billion ‘letters’ worth of information in every cell, there is a lot to scan for errors. However, unbroken DNA conducts electricity, while an error blocks the current. Now Dr Barton has found that some repair enzymes exploit this. One pair of enzymes lock onto different parts of a DNA strand. One of them sends an electron down the strand. If the DNA is unbroken, the electron reaches the other enzyme, and causes it to detach. I.e. this process scans the region of DNA between them, and if it’s clean, there is no need for repairs. But if there is a break, the electron doesn’t reach the second enzyme. This enzyme then moves along the strand until it reaches the error, and fixes it. This mechanism of repair seems to be present in all living things, from bacteria to man 1

This is another striking example of ingenious design inside the cell which points to an intelligent creator that made all living things. Its evident that the repair mechanism is essential for the cell to survive. It could not have evolved after life arose, but must have come into existence before. The mechanism is highly complex and elaborated, as consequence, the design inference is justified and seems to be the best way to explain its existence. Error can never be detected without an obligatorily preceeding knowledge or convention on what is correct.

DNA Damage and Electricity
March 8, 2015
Critical enzymes that repair DNA have an electrical mechanism involving clusters of iron and sulfur. These metallic clusters allow proteins that are part of the genetic and epigenetic complexes to move electrons. These same clusters operate in many other biological processes including photosynthesis and mitochondrial energy production. Since this research is just beginning, other electric mechanisms could be involved in the complex function of DNA. Do these electrical properties allow DNA networks to respond instantly to mind? How important are these newly discovered electrical properties of DNA and are they related to a theory that electromagnetic forces connect mind, matter and brain? What is the relation of electric DNA and mind? 5

DNA is assaulted all day by photons from the sun and chemicals in the cell’s environment, often causing damage. Copying DNA billions of times per day, also, produces errors. To fix DNA errors, first the cell must be able to identify them. The errors can be DNA that is altered, replaced, mismatched or missing. Like protein folding where the greatest super computers cannot determine how the fold should occur, no one knows how these errors can possibly be found given the number of molecules to check.

Special proteins are used to locate the damage among billions of nucleotide pairs. These proteins ride along the DNA looking for errors. Up until now there has been no way to understand how these molecules can find one missing link out of billions. This has to be done very rapidly. There is not enough time to examine each strand. The proteins just aren’t fast enough. Now, unique electric properties have been found in DNA that appears to allow the rapid detection of errors. One newly discovered property of DNA is that molecule conducts electricity as a wire. Very recently, this property has been linked to the ability of the cell to find abnormal spots for repair. DNA’s electrical properties allow protein to produce electrons that travel along the DNA wire.

DNA conducts electricity a very long distance—hundreds of nucleotide bases. Proteins on the other hand only produced tiny currents noted in the quantum effects of tunneling, which appear to be related to enzyme mechanisms. What has been striking about this new DNA research is that the electric current in DNA occurs when all of nucleotides have no errors. In this situation, the arrays of aromatic electron clouds create the currents, which travel for very long distances. If there are mismatches of the nucleotides through errors, such as missing, mismatched, or altered nucleotides, the current is disrupted.

One of the complex enzymes that repair DNA is endonuclease III, which uses base excision repair (BER) described in a previous post. It identifies the error and cuts out the damaged nucleotides and then calls for other enzymes to insert the correct ones. These large enzymes create complexes together for this work. This enzyme uses a complex of iron and sulfur atoms that are very involved in electron transfer processes. These metals can either take or give an electron known as reduction and oxidation in chemistry.

When connected to DNA, Endonuclease III changes its shape allowing the iron and sulfur atoms to give up electrons increasing its charge. This shape alteration makes the enzyme increase its hold on the DNA. The released electron travels along the DNA wire until it meets another Endonuclease III molecule attached to the DNA. The second Endonuclease III molecule takes up the electron from the DNA. Taking up this electron, the second enzyme loosens its grip on the DNA.

As the electron travels along the DNA wire, it is stopped if there is a damaged spot, thus identifying a problem. When the error is identified, both of the repair molecules stay attached to the DNA wire on either side of the error, identifying a trouble spot. In fact, Endonuclease III does more. It helps communicate with other proteins, such as MutY, that come and fix the mutation.

This is all mind-boggling and fascinating and shows how much care the Creator has had to make sure that DNA mutations remain on a minimal level, and are removed by incredibly advanced error check and repair mechanisms, as the one described here.

Location of DNA damage by charge exchanging repair enzymes: effects of cooperativity on location time
How DNA repair enzymes find the relatively rare sites of damage is not known in great detail. Recent experiments and molecular data suggest that individual repair enzymes do not work independently of each other, but interact with each other through charges exchanged along the DNA. A damaged site in the DNA hinders this exchange. The hypothesis is that the charge exchange quickly liberates the repair enzymes from error-free stretches of DNA. In this way, the sites of damage are located more quickly 2

New Scientists : Enzymes scan DNA using electric pulse
ENZYMES that repair DNA may check for mutations by sending electrons along sections of the strand, in much the same way that electricians test for faults in circuits. The mechanism might explain how enzymes locate problems in the genome fast enough to correct them. Most genetic mutations are caused by free radicals scavenging electrons from DNA. This "oxidative damage" introduces errors such as base-pair mismatches when the strand replicates. If these errors build up they can be extremely harmful. All organisms have enzymes that can repair the errors. They bind to DNA and are thought to move slowly along the strand, testing each base pair to see if there is a mismatch. But Jacqueline Barton of the California Institute of Technology in Pasadena is not convinced this is what happens. "That would take a lot of time," she says - too long to allow the genome to be comprehensively scanned. ... 3

DNA-mediated charge transport for DNA repair
August 15, 2003

The [4Fe4S] cluster of these base excision repair enzymes, containing a unique ligating peptide sequence, is thus well designed for its function: robust in solution as [4Fe4S], stable to oxidizing and reducing conditions of the cell, but, once buried within DNA, activated to carry out redox chemistry. Importantly, our electrochemical data indicate that DNA-mediated charge transport (CT) CT involving the [4Fe4S] cluster of MutY is feasible. The primary lesson learned from our many studies of DNA CT chemistry is that DNA CT is exquisitely sensitive to perturbations in base pair structure . Indeed we have shown DNA CT electrochemistry as a diagnostic tool for mutations and lesions in DNA. Might DNA repair proteins, MutY in particular, similarly exploit DNA CT to detect mismatches and lesions in DNA?

Based on results of others, within the cell, MutY contains a [4Fe4S]2 cluster . On binding DNA nonspecifically, as our results indicate, MutY undergoes a shift in redox potential, and the 32 couple becomes accessible, so that the
cluster may become oxidized and release an electron in a DNA-mediated reaction. Upon oxidation, MutY could then serve, through DNA-mediated charge transport (CT), to reduce an alternate DNA repair protein, perhaps another MutY, bound at a distant site a along the duplex. The electrochemistry data indicate that such a DNA-mediated process is possible. Moreover, association of two MutY equivalents on the DNA template has been proposed based on kinetic experiments . In the reduced form, the DNA affinity of MutY should be diminished, facilitating dissociation of the protein from its DNA site. We propose that this process, as described, constitutes a scan of this region of the
genome. The CT scanning mechanism does not obviate these schemes. Instead, the DNA CT scanning strategy confines the search to a manageable regime within the genome. Furthermore, although the specificity ratio, 10–1,000, of these repair proteins for their target site versus well-matched DNA is too low to explain preferential recognition of mismatches within the genome, this small level of specificity is sufficient for target binding within the subset of mismatch-containing strands. 4

1) http://creation.com/electric-dna#endRef5
2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142343/
3) http://www.newscientist.com/article/mg18024171.200-enzymes-scan-dna-using-electric-pulse.html
4) http://authors.library.caltech.edu/627/1/BOOpnas03.pdf
5. http://jonlieffmd.com/blog/human-brain/electric-dna-mind

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Otangelo · 9 DNA could not survive without repair mechanisms. Sun Jul 05, 2015 7:05 pm

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DNA could not survive without repair mechanisms.

http://www.icr.org/article/few-reasons-evolutionary-origin-life-impossible/

DNA, as is true of messenger-RNA, transfer-RNA, and ribosomal-RNA, is destroyed by a variety of agents, including ultraviolet light, reactive oxygen species, alkylting agents, and water. A recent article reported that there are 130 known human DNA repair genes and that more will be found. The authors stated that "Genome |DNA| instability caused by the great variety of DNA-damaging agents would be an overwhelming problem for cells and organisms if it were not for DNA repair emphasis mine)."6 Note that even water is one of the agents that damages DNA! If DNA somehow evolved on the earth it would be dissolved in water. Thus water and many chemical agents dissolved in it, along with ultraviolet light would destroy DNA much faster than it could be produced by the wildest imaginary process. If it were not for DNA repair genes, the article effectively states, DNA could not survive even in the protective environment of a cell! How then could DNA survive when subjected to brutal attack by all the chemical and other DNA-damaging agents that would exist on the hypothetical primitive Earth of the evolutionists?

What are the cellular agents that are necessary for DNA repair and survival? DNA genes! Thus, DNA is necessary for the survival of DNA! But it would have been impossible for DNA repair genes to evolve before ordinary DNA evolved and it would have been impossible for ordinary DNA to evolve before DNA repair genes had evolved. Here we see another impossible barrier for evolution. Furthermore, it is ridiculous to imagine that DNA repair genes could have evolved even if a cell existed. DNA genes encode the sequences of the hundreds of amino acids that constitute the proteins that are the actual agents that are involved in DNA repair. The code in the DNA is translated into a messenger RNA (mRNA). The mRNA must then move to and be incorporated into a ribosome (which is made up of three different ribosomal RNAs and 55 different protein molecules). Each amino acid must be coupled to a transfer RNA specific for that amino acid, and the coupling requires a protein enzyme specific for that amino acid and transfer-RNA. Responding to the code on the messenger RNA and utilizing the codes on transfer RNA's, the appropriate amino acids, attached to the transfer RNAs, are attached to the growing protein chain in the order prescribed by the code of the messenger RNA. Many enzymes are required along with appropriate energy. This is only a brief introduction to the incredible complexity of life that is found even in a bacterium.

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Otangelo

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Why Error detection/correction Mechanisms Require Intelligence 1

The one thing I find myself repeatedly having to explain to Darwinists is that the very existence error detection/correction mechanisms within the genome not only pre-supposes intelligence but absolutely, totally requires pre-knowledge of correct system state.
For some reason, probably related to their other mental illnesses, the Darwinians never get this. They seem incapable of logical response to existing facts. Most of the people I know, including some of the very well known scientists that often attempt debate with Darwinists know this to be a salient fact. As soon as one puts forth simple, clear and logical evidence that their theory doesn’t add up it’s like their minds go into infinite loops and no further reasoning is possible. Their minds are put on HOLD.
Therefore, in the case of error detection/correction mechanisms in the genome here’s a little analogous test I thought up to help Darwinists figure out why the very existence of such mechanisms pre-suppose intelligence.
Test:

Write a coherent sentence in English on a piece of paper. Make it say around 20-30 words long. In the sentence you create make sure to include a good number of glaring grammatical and spelling errors.
Now, find a monolingual Chinese or (other such language not using the English alphabet) person and ask them to find and correct the mistakes.

Obviously they are not going to either find or correct anything at all, for the whole is gibberish to them.
Do you see? No pre-knowledge of English grammar, symbolism, spelling etc. necessarily equals no ability to either detect or correct error.
Do you see how the same principle applies to any such error trapping/correcting in any syntactic system – including biological ones like DNA/RNA?
Good.
Design is the inevitable and ONLY scientifically correct explanation. Period.
This is not hard.

Information in DNA also has transmission and error checking protocols used as well as the translation mechanisms of RNA. These, by default, cannot be acquired in mere matter. They must be designed.Error can never be detected without an obligatorily preceeding knowledge or convention on what is correct.

1) https://borne.wordpress.com/category/darwinismintelligent-design/page/3/

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New class of DNA repair enzyme discovered 1

When the structure of DNA was first discovered, scientists imagined it to be extremely chemically stable, which allowed it to act as a blueprint for passing the basic traits of parents along to their offspring. Although this view has remained prevalent among the public, biologists have since learned that the double helix is in fact a highly reactive molecule that is constantly being damaged and that cells must make unceasing repair efforts to protect the genetic information that it contains.
"It's a double-edged sword," said Brandt Eichman, associate professor of biological sciences and biochemistry at Vanderbilt University, who headed the research team that made the new discovery. "If DNA were too reactive then it wouldn't be capable of storing genetic information. But, if it were too stable, then it wouldn't allow organisms to evolve."
The DNA double-helix has a spiral staircase structure with the outer edges made from sugar and phosphate molecules joined by stair steps composed of pairs of four nucleotide bases (adenine, cytosine, guanine and thymine) that serve as the basic letters in the genetic code.
There are two basic sources of DNA damage or lesions: environmental sources including ultraviolet light, toxic chemicals and ionizing radiation and internal sources, including a number of the cell's own metabolites (the chemicals it produces during normal metabolism), reactive oxygen species and even water.
"More than 10,000 DNA damage events occur each day in every cell in the human body that must be repaired for DNA to function properly," said first author Elwood Mullins, a postdoctoral research associate in the Eichman lab.
The newly discovered DNA repair enzyme is a DNA glycosylase, a family of enzymes discovered by Tomas Lindahl, who received this year's Nobel prize for recognizing that these enzymes removed damaged DNA bases through a process called base-excision repair. It was the first of about 10 different DNA repair pathways that biologists have identified to date.
In base-excision repair, a specific glycosylase molecule binds to DNA at the location of a lesion and bends the double-helix in a way that causes the damaged base to flip from the inside of the helix to the outside. The enzyme fits around the flipped out base and holds it in a position that exposes its link to the DNA's sugar backbone, allowing the enzyme to detach it. After the damaged base has been removed, additional DNA-repair proteins move in to replace it with a pristine base.
Eichman and his collaborators discovered that a glycosylase called AlkD found inBacillus cereus -- a soil-dwelling bacterium responsible for a type of food poisoning called the "fried rice syndrome" -- works in a totally different fashion. It does not require base flipping to recognize damaged DNA or repair it.
Seven years ago, Eichman's group discovered that AlkD had a structure unlike any of the other glycosylases. The researchers determined that the enzyme was able to locate damaged DNA that has a positive electrical charge. This is the signature of alkylation, attaching chains of carbon and hydrogen atoms of varying lengths (methyl, ethyl etc.), to specific positions on the damaged base. Positively charged alkylated bases are among the most abundant and detrimental forms of DNA damage. However, they are highly unstable, which has made them very difficult to study.
Now the researchers have captured crystallographic snapshots of AlkD in the act of excising alkylation damage and have shown that the enzyme doesn't use base flipping. Instead, they have determined that AlkD forms a series of interactions with the DNA backbone at and around the lesion while the lesion is still stacked in the double helix. Several of these interactions are contributed by three amino acids in the enzyme that catalyze excision of the damaged base.
According to the researchers, the AlkD mechanism has some remarkable properties:

It can recognize damaged bases indirectly. AlkD identifies lesions by interacting with the DNA backbone without contacting the damaged base itself.
It can repair many different types of lesions as long as they are positively charged. By contrast, the base-flipping mechanism used by other glycosylases relies on a relatively tight binding pocket in the enzyme, so each glycosylase is designed to work with a limited number of lesions. AlkD doesn't have the same type of pocket so it isn't restricted in the same way. Instead, the catalytic mechanism that AlkD uses is limited to removing positively charged lesions.
It can excise much bulkier lesions than other glycosylases. Base excision repair is generally limited to relatively small lesions. A different pathway, called nucleotide excision repair, handles larger lesions like those caused by UV radiation damage. However, Eichman's team discovered that AlkD could excise extremely bulky lesions, such as the one caused by the antibiotic yatakemycin, which is beyond the capability of other glycosylases.

"Our discovery shows that we still have a lot to learn about DNA repair, and that there may be alternative repair pathways yet to be discovered. It certainly shows us that a much broader range of DNA damage can be removed in ways that we didn't think were possible," said Eichman. "Bacteria are using this to their advantage to protect themselves against the antibacterial agents they produce. Humans may even have DNA-repair enzymes that operate in a similar fashion to remove complex types of DNA damage. This could have clinical relevance because these enzymes, if they exist, could be reducing the effectiveness of drugs designed to kill cancer cells by shutting down their ability to replicate."

1) http://www.sciencedaily.com/releases/2015/10/151029190840.htm

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Error checking - evidence of design

https://iaincarstairs.wordpress.com/about/

To make matters worse, the materialists, championed by outspoken critics of religion such as Richard Dawkins, put all biological development down to random mutations and declare the universe a blind and aimless place in which consciousness is a meaningless byproduct. But the cellular processes within the human body reproduce perfectly hundreds of trillions of times from the starting point as a single cell, and manufacture and error check trillions of complicated proteins and assembly devices over the course of a lifetime.

So, what we witness every day, what passes without comment in all living beings (which should be subject to the same physical tendencies as all such processes in the past) shows no sign of random wanderings at all, in fact, quite the reverse: the error checking procedures are so sophisticated that a tiny manufacturing error of a single wrongly placed amino acid can be detected in a device such as connectin which has 26,9216 precisely placed amino acid components, the entire assembly sent back, stamped for disassembly, and the parts recycled. How such an elaborate error detection system, filled with safeguards and protective devices, a system needed to maintain all biological life can itself arise from mistakes, faults, errors and other disasters – a single one of which can bring an intact human being to its knees in agony – seems impossible to imagine.

http://en.wikipedia.org/wiki/DNA_repair

Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when so-called "non-essential" genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.

http://creation.com/how-life-works

The only reason that DNA functions as well as it does is that cells come equipped with an amazing array of cooperative DNA repair mechanisms. For example, polymerase replication during cell division might produce 6 million errors per cell, but then proofreading machinery can reduce this to 10,000 and then mis-match repair machinery could reduce this to 100.

http://www.nature.com/scitable/topicpage/dna-damage-repair-mechanisms-for-maintaining-dna-344

Because DNA is the repository of genetic information in each living cell, its integrity and stability are essential to life. DNA, however, is not inert; rather, it is a chemical entity subject to assault from the environment, and any resulting damage, if not repaired, will lead to mutation and possibly disease. Perhaps the best-known example of the link between environmental-induced DNA damage and disease is that of skin cancer, which can be caused by excessive exposure to UV radiation in the form of sunlight (and, to a lesser degree, tanning beds). Another example is the damage caused by tobacco smoke, which can lead to mutations in lung cells and subsequent cancer of the lung. Beyond environmental agents, DNA is also subject to oxidative damage from byproducts of metabolism, such as free radicals. In fact, it has been estimated that an individual cell can suffer up to one million DNA changes per day (Lodish et al., 2005).

During the cell cycle, checkpoint mechanisms ensure that a cell's DNA is intact before permitting DNA replication and cell division to occur. Failures in these checkpoints can lead to an accumulation of damage, which in turn leads to mutations.

CPDs and 6-4 PPs are both repaired through a process known as nucleotide excision repair (NER). In eukaryotes, this complex process relies on the products of approximately 30 genes.

http://en.wikipedia.org/wiki/Nucleotide_excision_repair

Nucleotide excision repair is a DNA repair mechanism. [2] DNA damage occurs constantly because of chemicals (ie intercalating agents), radiation and other mutagens.

Additional DNA Repair mechanisms

NER and photoreactivation are not the only methods of DNA repair. For instance, base excision repair (BER) is the predominant mechanism that handles the spontaneous DNA damage caused by free radicals and other reactive species generated by metabolism

Thus, enzymes known as DNA glycosylases remove damaged bases by literally cutting them out of the DNA strand through cleavage of the covalent bonds between the bases and the sugar-phosphate backbone. The resulting gap is then filled by a specialized repair polymerase and sealed by ligase. Many such enzymes are found in cells, and each is specific to certain types of base alterations.

DNA glycosylases

http://en.wikipedia.org/wiki/DNA_glycosylase

DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond.

there is ‘base excision repair’: special enzymes called DNA glycosylases run down the DNA molecule, detect the damaged ‘letter’, grab it, put it in a specially shaped pocket, then chop it out. Then other enzymes repair the resulting gap.

Yet another form of DNA damage is double-strand breaks, which are caused by ionizing radiation, including gamma rays and X-rays. These breaks are highly deleterious. In addition to interfering with transcription or replication, they can lead to chromosomal rearrangements, in which pieces of one chromosome become attached to another chromosome. Genes are disrupted in this process, leading to hybrid proteins or inappropriate activation of genes. A number of cancers are associated with such rearrangements. Double-strand breaks are repaired through one of two mechanisms: nonhomologous end joining (NHEJ) or homologous recombination repair (HRR). In NHEJ, an enzyme called DNA ligase IV uses overhanging pieces of DNA adjacent to the break to join and fill in the ends. Additional errors can be introduced during this process, which is the case if a cell has not completely replicated its DNA in preparation for division. In contrast, during HRR, the homologous chromosome itself is used as a template for repair.

http://en.wikipedia.org/wiki/Non-homologous_end_joining

http://www.ncbi.nlm.nih.gov/pubmed/18166982

Mutations in an organism's DNA are a part of life. Our genetic code is exposed to a variety of insults that threaten its integrity. But, a rigorous system of checks and balances is in place through the DNA repair machinery.

http://creation.com/DNA-repair-enzyme

Shapiro, J.A., A Third Way, Boston Review, p. 2, February/March 1997

all cells from bacteria to man possess a truly astonishing array of repair systems which serve to remove accidental and stochastic sources of mutation. Multiple levels of proofreading mechanisms recognize and remove errors that inevitably occur during DNA replication. … cells protect themselves against precisely the kinds of accidental genetic change that, according to conventional theory, are the sources of evolutionary variability. By virtue of their proofreading and repair systems, living cells are not passive victims of the random forces of chemistry and physics. They devote large resources to suppressing random genetic variation and have the capacity to set the level of background localized mutability by adjusting the activity of their repair systems.

http://www.creationscience.com/onlinebook/LifeSciences39.html

DNA cannot function without hundreds of preexisting proteins,but proteins are produced only at the direction of DNA. Because each needs the other, a satisfactory explanation for the origin of one must also explain the origin of the other. Therefore, the components of these manufacturing systems must have come into existence simultaneously. This implies creation.

In each human, tens of thousands of genes are damaged daily!e Also, when a cell divides, its DNA at times is copied with errors. Every organism has machinery that identifies and repairs damaged and mistranslated DNA. Without such repair systems, the organism would quickly deteriorate and die. If evolution had happened, each organism would have become extinct before these DNA repair mechanisms could evolve.

Life’s complexity is mind boggling—not something that random processes could ever produce.

http://www.evolutionnews.org/2014/01/molecular_machi_3081111.html

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

it stops and waits. The problem is, when it stops, it stalls over the break, preventing repair machines from reaching it. Not to worry. Everything is under control.

In the new study, the NYU School of Medicine researchers reveal how another enzyme called UvrD helicase acts like a train engine to pull the RNA polymerase backwards and expose the broken DNA so a repair crew can get to work....

The study by Dr. Nudler's group and colleagues in Russia used a battery of biochemical and genetic experiments to directly link UvrD to RNA polymerase and to demonstrate that UvrD's pulling activity is essential for DNA repair. The lab results also suggest that UvrD relies on a second factor, called NusA, to help it pull RNA polymerase backwards. Those two partners then recruit a repair crew of other proteins to patch up the exposed DNA tracks before the train-like polymerase continues on its way.

Each of these machines is powered by ATP and built by the same DNA that it repairs! One can't help but recall Dean Kenyon's reaction in Unlocking the Mystery of Life to this kind of discovery: "This is absolutely mind-boggling to perceive, at this scale of size, such a finely-tuned apparatus, a device that bears the mark of intelligent design and manufacture." Each of these machines is complex enough in itself. To see them working as a cooperative team is all the more wonderful.

More on how a mystery was solved by the researchers at NYU:

According to Dr. Nudler, his team's study offers a convincing justification for a puzzling phenomenon known as pervasive transcription, which he calls "one of the most enigmatic and debated subjects of molecular biology." The question, he says, boils down to this: Why do RNA polymerases transcribe most of the genome within humans and other organisms, converting vast stretches of DNA to RNA, when only a tiny fraction of those resulting RNA transcripts will ever prove useful? Isn't that RNA polymerase activity a waste of energy and resources?

"Our results imply that a major role of RNA polymerase is to patrol the genome for DNA damage," he says. "This is the only molecular machine that is capable of continuously scanning the chromosomes for virtually any deviation from the canonical four bases in the template strand: A, T, G and C." The polymerase's extensive transcription activity, then, might be well worth the effort if its continuous vigilance also ensures that any DNA damage gets fixed through the assistance of the pulling factors and other collaborators.

So it wasn't wasteful after all. And we know from the ENCODE project that most (if not all) of the non-protein-coding DNA is important for regulation and other functions. This amplifies the importance of RNA polymerase's constant "vigilance" in inspecting the entire genome.

Included in the article are descriptions of bad consequences when RNA polymerase, UvrD helicase and the other machines don't work properly (perhaps due to mutations in their genes). Hair can turn brittle; children may age prematurely; others may suffer from exposure to sunlight. Those are the lucky ones who don't die without this vital repair mechanism.

The study reveals a "major new role of RNA polymerase and other enzymes in DNA repair." Notably, it's not the only repair system. Our genomes are protected by multiple levels of monitoring and repair, so that most of us carry on from day to day, completely oblivious of the multiple information-guided processes in our cells that make life work. There are systems that can fix double-stranded breaks. There are systems that can replace incorrect DNA bases (letters) in the code. There are even machines that can push the panic button when errors are catastrophic, causing a damaged cell to shut down.

For science to comprehend these systems, it needs a framework fit for the information age. It needs familiarity with robotics and multi-level control. The biology of Charles Darwin's antiquated Victorian world, which imagined systems emerging from unguided processes, is hopelessly inadequate. Darwin did not foresee, and could not have fathomed, the technology at the basis of life.

Otangelo · 13 DNA Search and Rescue Machine Imaged in Action Sat Jan 30, 2016 3:13 am

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DNA Search and Rescue Machine Imaged in Action

DNA is amazing enough, but its automatic error-correction utilities are enough to stagger the imagination. There are dozens of repair mechanisms to shield our genetic code from damage; one of them was portrayed in Nature1 March 31 (see also analysis by Sheila David in the same issue2) in terms that should inspire awe.
Imagine a huge encyclopedia written on beads, in strands many miles long. The words of the book are inscribed in letter beads along the strand. Now imagine that, tied to the primary strand, is a twin strand with beads representing the “negatives” of the primary beads, such that when the strands are separated, exact copies can be made. Every once in awhile, the strands are separated by a machine. Floating beads are attracted to the negative beads, lining up to form exact copies of the book or portions thereof. This is a simplified view of DNA transcription and replication. What happens, however, if the wrong bead, or a defective bead, becomes attached to the negative? For books, that could misspell a word or produce gibberish, but in living organisms, the consequences could be disastrous.
Now picture little machines that regularly traverse the string of beads. Because the shapes of the beads differ according to the letters on them, this machine is able to find typos. Let’s say that a letter “C” is always supposed to pair with a letter “G” on the strand. The proofreading machine feels every bead, and if it finds that particular mismatch, it ejects the incorrect bead so that another correct one can be fastened on by another machine. This is a simplified view of “base-excision repair” (BER) that actually takes place in your body, all the time.

The strands in a cell are, of course, DNA, and the beads are called nucleotides, or bases. Of the four bases in DNA (C, G, A, and T) cytosine or C is always supposed to pair with guanine, G, and adenine, A, is always supposed to pair with thymine, T. The enzyme studied by Banerjee et al. in Nature is one of a host of molecular machines called BER glycosylases; this one is called human oxoG glycosylase repair enzyme (hOGG1), and it is specialized for finding a particular type of error: an oxidized G base (guanine). Oxidation damage can be caused by exposure to ionizing radiation (like sunburn) or free radicals roaming around in the cell nucleus. The normal G becomes oxoG, making it very slightly out of shape. There might be one in a million of these on a DNA strand. While it seems like a minor typo, it can actually cause the translation machinery to insert the wrong amino acid into a protein, with disastrous results, such as colorectal cancer. This little machine has an important job.3 How does it work?
The machine latches onto the DNA double helix and works its way down the strand, feeling every base on the way. As it proceeds, it kinks the DNA strand into a sharp angle. It is built to ignore the T and A bases, but whenever it feels a C, it knows there is supposed to be a G attached. The machine has precision contact points for C and G. When the C engages, the base paired to it is flipped up out of the helix into a slot inside the enzyme that is finely crafted to mate with a pure, clean G. If all is well, it flips the G back into the DNA helix and moves on. If the base is an oxoG, however, that base gets flipped into another slot further inside, where powerful forces yank the errant base out of the strand so that other machines can insert the correct one.

Now this is all wonderful stuff so far, but as with many things in living cells, the true wonder is in the details. The thermodynamic energy differences between G and oxoG are extremely slight – oxoG contains only one extra atom of oxygen – and yet this machine is able to discriminate between them to high levels of accuracy. David says, “DNA-repair enzymes amaze us with their ability to search through vast tracts of DNA to find subtle anomalies in the structure. The human repair enzyme 8-oxoguanine glycosylase (hOGG1) is particularly impressive in this regard because it efficiently removes 8-oxoguanine (oxoG), a damaged guanine (G) base containing an extra oxygen atom, and ignores undamaged bases” (emphasis added in all quotes). The team led by Anirban Banerjee of Harvard, using a clever new stop-action method of imaging, caught this little enzyme in the act of binding to a bad guanine, helping scientists visualize how the machinery works.
Some other amazing details are mentioned about this molecular proofreader. It checks every C-G pair, but slips right past the A-T pairs. The enzyme, “much like a train that stops only at certain locations,” pauses at each C and, better than any railcar conductor inspecting each ticket, flips up the G to validate it. Unless it conforms to the slot perfectly – even though G and oxoG differ in their match by only one hydrogen bond – it is ejected like a freeloader in a Pullman car and tossed out into the desert. David elaborates:

Calculations of differences in free energy indicate that both favourable and unfavourable interactions lead to preferential binding of oxoG over G in the oxoG-recognition pocket, and of G over oxoG in the alternative site. This structure [the image resolved by the scientific team] captures an intermediate that forms in the process of finding oxoG, and illustrates that the damaged base must pass through a series of ‘gates’, or checkpoints, within the enzyme; only oxoG satisfies the requirements for admission to the damage-specific pocket, where it will be clipped from the DNA. Other bases (C, A and T) may be rejected outright without extrusion from the helix because hOGG1 scrutinizes both bases in each pair, and only bases opposite a C will be examined more closely.

How many linemen does it take to repair your strands? The researchers explain, “Only 50,000 molecules of hOGG1 protect the entire 6 x 109 base-pair nuclear genome of a diploid human cell, hence the enzyme must have developed an efficient mechanism for distinguishing oxoG from the four nucleobases in normal DNA.” 50,000 repairmen for 6 billion bases: that’s one repairman for every 120,000 letters, comparable to a skilled proofreader checking every letter of a 20,000 word document for one specific kind of typo. Then there are all the other proofreaders that look for other kinds of mistakes.4

¹Banerjee et al., “Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA,” Nature 434, 612 - 618 (31 March 2005); doi:10.1038/nature03458.
²Sheila S. David, “Structural biology: DNA search and rescue,” Nature 434, 569 - 570 (31 March 2005); doi:10.1038/434569a.
³See “Life without DNA Repair,” in PNAS, 1997. It lists 13 BER enzymes including this one. Studies on mice are described: “mutants show various combinations of defective embryogenesis, tissue-specific dysfunction, hypersensitivity to DNA-damaging agents, premature senescence, genetic instability, and elevated cancer rates.”
⁴The authors mention another paralogous enzyme, 3-methyladenine DNA glycosylase (AlkA), which is not as “fastidious” as hOGG1, because it “does occasionally excise adenine residues from undamaged DNA.” But there may be reasons for the differences in fidelity; some may have to work under stressful conditions, and repair as much as they can within constraints of time or other factors. JBC Online says that AlkA has “a remarkably versatile active site.” This reminds us that intelligent design does not mean perfection of every detail, but “constrained optimization”: achieving the combination of features that produces a “sweet spot” with best overall performance. The proof of the pudding for DNA repair is in the performance itself: no one watching a race horse, cormorant (05/24/2004) or champion triathlete in action could argue with the assertion that the suite of repair enzymes in living things appears optimized to achieve an extremely high degree of fidelity under a wide range of conditions and stress factors.

OK, Darwin Party: checkmate. Natural selection cannot act without accurate replication, yet the protein machinery for the level of accuracy required is itself built by the very genetic code it is designed to protect. Explain that! If the Darwinists cannot provide a plausible mechanism whereby nonliving chemicals, by chance, hit upon a means of replicating information-bearing molecules accurately, there would have been no evolution, because any gains would have been drowned in the errors of subsequent generations.
It would have been challenging enough to explain accurate translation alone in a primordial soup, but now throw in some free radicals and radiation, and any information gained would have quickly been destroyed through accumulation of errors. So accurate replication and proofreading are required for the origin of life. How on earth could proofreading enzymes emerge, especially with this degree of fidelity, when they depend on the very information that they are designed to protect? Think about it. This is a catch-22 for Darwinists. No wonder none of the authors of these two articles dared whisper the word evolution. The gig is up; we might as well not even waste any time arguing about Hobbit man (03/25/2005), peppered mice (04/18/2003) and what IMAX films to show (03/23/2005). Proofreading codes by chance? And a complex suite of translation machinery without a designer? Anyone with a head screwed on is not going to want such nonsense taught in public schools (03/24/2005).
If we can just sweep away the cobwebs of musty Darwinian thinking out of our minds for a moment, we can begin to enjoy the wonder of these incredible mechanisms. If the ancients could understand that creation demands a Creator by looking at the sun, or a bird, or a baby, how much more we today with all the revelations about cell biology and molecular machines? The grand oratorio of creation is being unveiled, a little at a time, into a hallelujah chorus that deserves our most worshipful applause – indeed, a standing ovation.

http://creationsafaris.com/crev200503.htm

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Error checking and repair systems in the cell, amazing evidence of design DNA_repair_enzyme

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Otangelo · 15 Cell Repairs its RNA, Too Sat Jan 30, 2016 3:53 am

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Cell Repairs its RNA, Too

The cell has elaborate ways to safeguard its genetic library by repairing DNA, but now scientists are finding the same enzymes can also repair RNA. In the Feb. 20 issue of Nature, Begley and Samson of MIT discuss the findings of Aas et al that RNA methylation damage can be repaired by the same AlkB enzyme that repairs DNA. This is surprising because RNA and proteins were considered more expendable than DNA, but they explain why it makes sense (emphasis added):

Why, though, should it be necessary to repair damaged RNA? The answer could be that although DNA is the final arbiter of genetic information, RNA is essential for the most basic biological processes. RNA-based primer sequences are required for DNA replication; and mRNAs, transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) are all needed during the elaborate process of protein synthesis. Even the formation of peptide bonds by ribosomes (the cell’s protein-making machines) turns out to require catalysis mediated by rRNAs. Moreover, a battery of small, non-protein-coding RNAs regulates a variety of other cellular processes.
So maintaining RNA integrity is important for proper cellular function. And repairing damaged RNA may be more efficient than destroying it and starting again. Ribosome assembly is a complex, energy-intensive process, and it is not hard to imagine that the thrifty repair of damaged rRNA would be preferable to disassembling or discarding an entire ribosomal particle.

Another surprise is that the repair mechanism seems to be able to distinguish between DNA and RNA, and between toxic methylation damage and normal biological methyl groups attached to some RNAs. Begley and Samson think it not unlikely that DNA and RNA might overlap in other ways, such as in cell signalling.
Update 06/16/2003: In the June 17 issue of Current Biology, Alfonso Bellacosa and Eric G. Moss from the Fox Chase Cancer Center in Philadelphia remind us that “RNA in a cell is subject to many of the same insults as DNA“ and that “the ‘information content’ of cellular RNA is greater than that of the chromosomal DNA” because almost all of RNA’s sequences have functional significance (messenger RNA and transfer RNA), whereas only 3% of the DNA has coding potential. Since RNA shows significant response to anticancer agents, the authors suppose that newly-discovered RNA repair pathways are important for preventing cancer:

A cell has a great investment in its RNAs – they are working copies of its genomic information. The study of mRNA biogenesis in the last few years has revealed an elaborate surveillance mechanism involving factors such as the UPF proteins that culls aberrantly spliced mRNAs and mRNAs with premature termination codons. There might be a hint that such RNA quality control mechanisms go awry in cancers, just as DNA quality control mechanisms do, where aberrantly spliced transcripts accumulate in a tumor. Now that the gates are open, we may have a flood of studies on the RNome [the RNA genome] stability and cancer.

This aggravates the chicken-and-egg problem for proponents of natural mechanisms. In the “RNA World” hypothesis for the origin of life, RNA performed both the information storage and enzymatic functions before these roles were outsourced to DNA and proteins. But how could RNA repair itself? If RNA needs to be protected from damage, the protein repair system would have needed to be there from the beginning. Proponents of natural mechanisms might surmise that different primitive RNAs worked side by side to repair each other, but that strains credibility for a hypothesis already far-fetched.
In typical evolutionary lingo, Begley and Samson blow smoke about what nature produced (emphasis added): “It seems that, for each human protein, parameters have evolved to distinguish between RNA and DNA,” they speculate, and in another place, “It might be that the RNA-demethylation activity of AlkB-like proteins evolved to regulate biological RNA methylation, and that the repair of aberrant, chemical methylation is fortuitous.” Ask them how the cell evolved these things, and you’ll probably get a quizzical look, as if “Why are you asking such a dumb question? I don’t know. It just had to. We’re here, aren’t we?”

http://creationsafaris.com/crev0203.htm

Error checking and repair systems in the cell, amazing evidence of design RNA_fix

Error checking and repair systems in the cell, amazing evidence of design RNA_fix

Error checking and repair systems in the cell, amazing evidence of design RNA_fix1

Error checking and repair systems in the cell, amazing evidence of design RNA_fix12

Error checking and repair systems in the cell, amazing evidence of design RNA_fix123

Otangelo · 16 Electric DNA and Mind Sat Feb 06, 2016 2:32 pm

Many Forms of Brain Electricity

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New instruction manual discovered for repairing broken DNA 1

Drexel University and Georgia Institute of Technology researchers have discovered how the Rad52 protein is a crucial player in RNA-dependent DNA repair. The results of their study, published in Molecular Cell, reveal a surprising function of the homologous recombination protein Rad52. They also may help to identify new therapeutic targets for cancer treatment.

Radiation and chemotherapy can cause a DNA double-strand break, one of the most harmful types of DNA damage. The process of homologous recombination — which involves the exchange of genetic information between two DNA molecules — plays an important role in DNA repair, but certain gene mutations can destabilize a genome. For example, mutations in the tumor suppressor BRCA2, which is involved in DNA repair by homologous recombination, can cause the deadliest form of breast and ovarian cancer. Paper. (paywall) – Olga M. Mazina, Havva Keskin, Kritika Hanamshet, Francesca Storici, Alexander V. Mazin. Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Molecular Cell, 2017

Collaborative Dynamic DNA Scanning by Nucleotide Excision Repair Proteins Investigated by Single-Molecule Imaging of Quantum-Dot-Labeled Proteins 2
2014 Apr 15
One of the fundamental questions in the field of DNA repair is how a modest number of repair proteins scan through several million (for bacteria) to a few billion (for mammalian cells) base pairs of nondamaged DNA to find rare damaged bases. How proteins locate their cognate recognition sequences has been extensively studied over the years , and several modes of searching have been hypothesized and recently reviewed. It is generally believed that facilitated diffusion in a one-dimensional (1D) search greatly enhances the rate of site location. However, direct sliding along DNA could be hampered by the numerous proteins bound to DNA inside a living cell. Thus, other searching modes such as hopping or intersegmental transfer have been proposed.
Nucleotide excision repair (NER) is a generalized DNA repair system capable of recognizing and removing a diverse array of chemical and physical DNA lesions, such as UV-induced photoproducts and carcinogen-DNA adducts. This highly conserved process is mediated by the concerted action of several proteins. NER is initiated by DNA distortion detection and then followed by:

(1) damage verification,
(2) coordinated incisions,
(3) excision of an oligonucleotide containing the damaged base,
(4) repair synthesis, and
(5) ligation.

In humans, a deficiency in any one of the 7 out of the ~30 NER proteins required for efficient repair can lead to the syndrome xeroderma pigmentosum, characterized by high incidence of skin cancer and, in some cases, neurodegeneration. UvrA and UvrB are the proteins that mediate damage recognition during NER. Approximately 20–50 copies of UvrA and UvrB are normally found per E. coli cell; however, SOS response induction mediated by LexA results in a further 5- to 10-fold induction of the UvrA and UvrB proteins The crystal structures and function analysis of UvrA, UvrB, and UvrC have helped delineate the molecular interactions and action mechanism of each protein during the coordinated damage recognition and repair process.
UvrA as a dimer interacts with UvrB to form either a UvrA2B or UvrA2B2 complex; for simplicity, we refer to these complexes as UvrAB hereafter. During damage recognition, UvrA is hypothesized to recognize helical distortions induced in the DNA rather than the actually modified nucleotide. UvrA initiates damage verification through derepression of an autoinhibitory domain (domain 4) on UvrB. UvrB engages the damaged site through a β-hairpin, causing dissociation of UvrA. UvrC then binds, producing dual incisions surrounding the damage. In the final steps of NER, DNA polymerase I and UvrD (helicase II) remove the post-incision complex and synthesize the repair patch, which is sealed by DNA ligase. Despite the structural and biochemical information available about these proteins, the dynamics of these interactions on DNA remain elusive. To help elucidate this problem, we have turned to single-molecule approaches, which have previously been successfully employed for the study of other DNA protein systems, including EcoRV diffusion on DNA; Rad51 involved in recombination; hOgg1, a glycosylase involved in base excision repair; and the action of mismatch repair heterodimer of Msh2-Msh6 .
We report here that damage recognition during NER involves an initial 3D search by UvrA, which collapses into a 1D search when UvrB is added. Unexpectedly, we have found that UvrAB has a complex motion on DNA and appears to display unbiased diffusion, directed motion, and paused motion. Finally, differential labeling of both UvrA and UvrB with different color Qdots has uniquely allowed direct visualization of a protein complex of two separate protein partners loading onto DNA and dissociating during the process of NER.

1. http://www.sciencedirect.com.sci-hub.cc/science/article/pii/S1097276517303593
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986923/

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The 2015 Nobel prize in Chemistry to scientists that discovered RNA & DNA repair mechanisms

The 2015 Nobel Prize in Chemistry has been awarded to three scientists for their truly amazing discoveries about the DNA code of life. An article from the Swedish Academy of Science highlights the significance of these discoveries for understanding how our cells can copy the DNA code millions of times with hardly ever making a mistake. 1 ( See article 32 )

DNA repair mechanisms are crucial to our existence. Without them, we would not survive because of DNA damage caused by the environment (e.g UV light damage, radiation etc.). 3

The cells’ toolbox for DNA repair
The Nobel Laureates in Chemistry 2015 have provided fundamental insights into how cells function. The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information.

In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.

Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.

Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer. 2

Several DNA repair pathways work in a complementary manner to eliminate lesions from DNA. 7

Different pathways for DNA repair exists,

Nucleotide excision repair (NER)
Base excision repair (BER)
DNA mismatch repair (MMR)
Repair through alkyltransferase-like proteins (ATLs) amongst others.

Nucleotide Excision Repair
Nucleotide excision repair is a generic repair process that requires several successive steps: recognition of the lesion, cleavage of the strand containing it, removal of an oligonucleotide, and resynthesis with high fidelity at the site. Commonly, incisions bracket the site of the lesions closely. This process is very highly conserved in the Bacteria, as the UvrABCD pathway, and has been studied in yeast and human where at least eight proteins have been identified with activities corresponding to the bacterial system. 6

Of all the known repair proteins, RecA/Rad51/RadA seems to be the only one present in every genome analyzed.

Modern mRNA Proofreading and Repair: Clues that the Last Universal Common Ancestor Possessed an RNA Genome?
February 27, 2014
Without some form of proofreading and repair, the number of mRNAs carrying coding errors could be significant. Leipe, Aravind, and Koonin (1999) suggest that LUCA possessed a hybrid DNA/RNA genome, thereby providing an explanation for the universal distribution of certain components of the DNA replication/repair apparatus. 5 We argue from structural and functional data that the second of these, RNA polymerase-dependent proofreading and repair, is likely to have been a feature of LUCA rather than a recent innovation as part of selection for improved messenger RNA (mRNA) quality control, though this is no doubt the current function of this phenomenon. The capacity for repair appears to be a consequence of the common two-metal mechanism for elongation which implies that, at the very least, the RNA polymerase in LUCA possessed the capacity for repair.

Error checking and repair systems in the cell, amazing evidence of design PROnvER

Error checking and repair systems in the cell, amazing evidence of design PROnvER

Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor
1, Mar. 2018
Without evidence of a pre-RNA system or such additional transitions, the simpler, uniformitarian hypothesis of a primordial RNA-based earliest life remains the most compelling. Both UV and ionizing radiation damage DNA and RNA. This damage can result in mutations or transcription errors that have significant, deleterious consequences for organisms at the cellular level. Organisms have evolved a variety of mechanisms to repair radiation damage to their genomes, and these mechanisms make it possible for organisms to thrive on Earth’s surface, exposed to ultraviolet light from the Sun. Radiation damage has strongly negative consequences for the stability and fidelity of genetic material, radiation exposure would present a significant challenge in the development of an early nucleotide-based system. Organisms have a variety of complex mechanisms to repair radiation damage. Excision repair of DNA in modern Escherichia coli makes use of six proteins; these proteins must be highly specific for DNA damage in order to avoid mutagenesis.

Comment: This paper begins in its abstract with the false claim that: Extensive fundamental molecular and biological evolution took place between the prebiotic origins of life and the state of the Last Universal Common Ancestor (LUCA) - when evolution cannot be claimed prior when DNA replication began. A grotesque error. Then, the authors continue claiming that the repair mechanisms of RNA and DNA evolved. That's an unsubstantiated claim. If the repair mechanisms were not fully developed and acting from day one, there would be no RNA and/or DNA lasting for enough time to do any job.

The paper continues:
This complexity makes their emergence in the early RNA world implausible. Without a known abiotic mechanism or catalyst to repair radiation damage, any scenario wherein RNA emerged in an environment with significant radiation flux seems unlikely. It has long been expected that UV flux would represent a challenge for early life on Earth’s surface. Even current solar UV radiation presents a significant challenge to modern microbes. Similar damage can occur from sources of ionizing radiation, so an origin of life within a radioactive, mineral-rich environment faces similar, if not even greater, challenges as an origin with direct exposure to UV.

UV is thought to have played at the same time a significant role in prebiotic synthesis, it plays a key role in the prebiotic synthesis of uracil and cytosine. It is difficult to define a threshold before which UV levels are critical for achieving prebiotic synthesis, but after which UV levels are too damaging to nucleic acids. Modern experiments exploring the role of UV-mediated prebiotic chemistry often use ultraviolet light of wavelength 254 nm due to the commercial availability of mercury lamps emitting light at this wavelength. Ultraviolet light between 200-280 nm (UVC) is today blocked by the modern atmosphere and ozone layer, it was likely a significant force on the early Earth.

Not only is the damage repaired by PHR caused by ultraviolet light, but the photolyases responsible for PHR rely on near-UV light to drive the repair reaction. The apparent paradox of UV as both a threat to life and aid for prebiotic chemistry is a further challenge for OOL investigators to explain. A UV flux sufficient to drive significant prebiotic synthesis would also damage RNA.

Clay minerals have long been proposed as potential sites for the accumulation and assembly of prebiotically significant chemicals. The clay mineral montmorillonite has been shown to protect the RNA molecule ADHR1 from UV-induced damage. One could speculate that such precursors could be more UV-resistant, and not experience the same environmental restrictions. However, moving from a UV-resilient pre-RNA system to a UV-sensitive RNA system would appear to be selectively disadvantageous. It requires that later stages of early life became more, not less environmentally constrained, which is highly unlikely.

Did Basic DNA Repair Mechanisms Evolve More Than Once ?
Comparative sequence analyses of proteins from the three domains of life prompted Eugene Koonin and coworkers to propose that DNA replication evolved twice independently, once in the bacterial lineage and the other in the archaeal/eukaryal lineage. Furthermore, the universal conservation of some components of the DNA repair machinery suggested that the LUCA had DNA, but did not replicate in the same way modern cells do. Leipe et al proposed that LUCA was actually a RNA-centered organism with a possible DNA replication intermediate. Regardless of the information storage mode, the enzymatic basis for nucleic acid repair of strand breaks, and recombination repair, must have been present in order to preserve the fidelity of information transfer from generation to generation.

1. https://factandfaith.co.za/other-articles/?fbclid=IwAR0dR4fBkeyaer17SSAodkSrBibWZ12Rh2Fr3Sdb61y78SQnfWyz-bdy9-Q
2. https://www.nobelprize.org/prizes/chemistry/2015/press-release/
3. https://labiotech.eu/medical/nobel-prize-2015-dna-repairing-mechanism-keeps-alive-rewarded/
4. https://webcache.googleusercontent.com/search?q=cache:apop8MuNB2gJ:https://dspace.mit.edu/openaccess-disseminate/1721.1/114219+&cd=4&hl=en&ct=clnk&gl=br
5. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.539.4745&rep=rep1&type=pdf
6. http://sci-hub.tw/https://link.springer.com/chapter/10.1007/0-387-26887-1_11
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC107647/

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Another amazing example of fine-tuning and the use of quantum mechanics in biochemistry !! Its origin, by unguided natural events, or intelligent design ?

The genomes of all cellular lifeforms and several large DNA viruses encode multiple proteins whose function is to repair the damaged DNA

DNA repair is essential for any organism, and for cellular function. Maintaining the genetic stability that an organism needs for its survival requires not only an extremely accurate mechanism for replicating DNA, but also mechanisms for repairing the many accidental lesions that occur continually in DNA.

DNA repair as a whole is a highly complex phenomenon. The repair mechanisms can be classified into several distinct, if not completely independent, major pathways that differ with regard to the level at which the lesions in damaged DNA are reversed or removed by the repair machinery

Endonucleases are a type of enzyme that cuts the phosphor-diester bond—the backbone of DNA—in a strand of DNA or RNA. Type I cuts the DNA bond randomly. There are many other specific versions called “restriction enzymes” that cut only at very specific sequences. Type III has been studied the most for its relation to electric DNA and cuts very specifically.

When connected to DNA, Endonuclease III changes its shape allowing the iron and sulfur atoms to give up electrons increasing its charge. This shape alteration makes the enzyme increase its hold on the DNA. The released electron travels along the DNA wire until it meets another Endonuclease III molecule attached to the DNA. The secondEndonuclease III molecule takes up the electron from the DNA. Taking up this electron, the second enzyme loosens its grip on the DNA.

As the electron travels along the DNA wire, it is stopped if there is a damaged spot, thus identifying a problem. When the error is identified, both of the repair molecules stay attached to the DNA wire on either side of the error, identifying a trouble spot. In fact, Endonuclease III does more. It helps communicate with other proteins, such as MutY, that come and fix the mutation.

This mechanism of exchanging electrons has now been shown to be extremely important in many techniques for repairing DNA. It, also, occurs occurs with many other repair proteins.

Now this is truly amazing:

How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases

Type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers.

The purpose of the orthodox class of these enzymes is to catalyze a double-strand break without the use of an external chemical energy source like ATP. Our hypothesis has been that these enzymes recruit this energy from coherent oscillations in the DNA substrate. In the absence of direct experimental confirmation, the computational data presented here provide tentative support that the coherent oscillations in six- and eight-base-pair DNA target sequences may be finely tuned for the energy sequestration that is required to initiate synchronized double-strand breakage.

One more example of fine-tuning in biochemistry. Amazing !!

Error checking and repair systems in the cell, amazing evidence of design Nihms-10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746125/

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Researchers Discover Sophisticated Hospital System For DNA In Cells
https://uncommondescent.com/intelligent-design/researchers-discover-sophisticated-hospital-system-for-dna-in-cells/?fbclid=IwAR2cZLb3uf4yZGpm5eMocKwzDA41_8flUecjc8xnGuif2A9_Hd9xDTAIOH0

An elaborate system of filaments, liquid droplet dynamics and protein connectors enables the repair of some damaged DNA in the nuclei of cells, researchers at the University of Toronto have found. The findings further challenge the belief that broken DNA floats aimlessly — and highlight the value of cross-disciplinary research in biology and physics.

Double-strand DNA breaks are especially toxic to cells, and researchers had assumed for decades that these breaks floated inside cell nuclei without direction, until they trigger other cellular changes or happen on a fixer mechanism.

That thinking began to change in 2015, when Karim Mekhail and his lab showed that damaged DNA can be intentionally transported by motor protein ‘ambulances’ to DNA ‘hospitals,’ areas enriched with certain repair factors in the nuclei. The researchers later worked with U of T aerospace engineers to show that after a single double-strand break, DNA travels for repair via long ‘autobahns’ of thread-like microtubules, which are also moving…

The most surprising finding came after several cycles of droplet fusion, the researchers found. “It was very bizarre and totally unexpected, I still remember the day,” Mekhail says. Oshidari observed that the larger droplets initiate an internal concentration of filament building blocks, forcing creation of a kind of self-interlocking brick road, which together with the spidery webs allow DNA to hook onto the longer autobahn filaments.

The complex process is easy to miss when looking at DNA damage sites, says Mekhail, largely because imaging in the field has become highly automated. Most software has been set up to see what has already been seen. “We can’t rely on the old ways of observing,” he says. “We need to update our software and also go back to looking with the human eye, guided by simulations when needed.” University of Toronto, “Genome stability: Intricate process of DNA repair discovered” at ScienceDaily

Genome stability: Intricate process of DNA repair discovered
February 5, 2020
https://www.sciencedaily.com/releases/2020/02/200205132349.htm

DNA repair by Rad52 liquid droplets
04 February 2020
https://www.nature.com/articles/s41467-020-14546-z

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Unraveling the genome in 3-D space

Proper folding of extremely long chromosomal DNA molecules is crucial for the correct functioning of the cell.
In order to fit into cells, chromosomal DNA is folded many times. But the DNA is not merely squeezed into the nucleus randomly but folded in a specific and highly regulated structure. The spatial organization of chromosomal DNA enables regulated topological interactions between distant parts, thereby supporting proper expression, maintenance, and transport of the genome across cell generations.

Breaks in DNA, which can occur spontaneously or result from irradiation or chemical insults, can lead to severe problems since they foster mutations and can ultimately lead to cancer. But not every DNA break has disastrous consequences, since cells have ingenious ways of repairing the damage. One of the main DNA repair pathways involves copying the missing information on the damaged DNA from the replicated sister chromatid. For this to occur, the two DNA molecules of sister chromatids need to come close together at the exact same genomic position. DNA molecules are organized relative to each other to support this important repair pathway.

A pool of cohesin that mediates linkage between replicated DNA molecules maintains the global alignment of sister chromatids after DNA replication, while a pool of cohesin that dynamically forms loops locally separates sister chromatids within TADs during G2.

Error checking and repair systems in the cell, amazing evidence of design 6-unravelingth

Error checking and repair systems in the cell, amazing evidence of design 6-unravelingth

Proper folding o

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Error check and repair mechanisms in protein synthesis

https://reasonandscience.catsboard.com/t2043-dna-and-rna-error-checking-and-repair-amazing-evidence-of-design#8341

The genome provides a precise biological blueprint of life. To implement this blueprint correctly, the genome must be transcribed with great precision.3
Protein synthesis is a complex, multistage process, and many things can go wrong along the way. A protein that has not been synthesized correctly may be non-functional or toxic. Many mechanisms minimize the costs of erroneous protein synthesis. 4

Accurate transcription is an essential step in accessing the genetic information stored in genes. In eukaryotes, transcription of DNA into mRNA is carried out by RNA polymerase II (Pol II), an enzyme comprised of 12 subunits. The net misincorporation rate is estimated to be about one per 100,000 bases. This reflects initial misincorporation by Pol II and subsequent editing mechanisms, some intrinsic to the core polymerase and others facilitated by transcription factors. 2

Amino acid misincorporations during translation are estimated to occur once in every 1,000 to 10,000 codons translated 5 There are even different error check and repair mechanisms during translation. Consider, that life cannot start, unless these mechanisms are fully in place, and operational. 6

Sources of errors in eukaryotic gene expression

Error checking and repair systems in the cell, amazing evidence of design Source10

We define erroneous protein synthesis as any disruption in the conversion of a coding sequence into a functioning protein. Besides amino-acid misincorporations, sources of errors are transcription errors, aberrant splicing, premature termination, faulty posttranslational modifications, and kinetic missteps during folding. This definition explicitly includes correctly synthesized polypeptides that fail to fold into a functional protein.Translation is the most error-prone step of protein synthesis.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764353/
2. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004532
3. https://advances.sciencemag.org/content/3/10/e1701484
4. https://www.nature.com/articles/nrg2662?proof=t
5. https://sci-hub.ren/10.1038/nrg2662
6. https://reasonandscience.catsboard.com/t2984-error-check-and-repair-during-messenger-rna-translation-in-the-ribosome-by-chance-or-design

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JMike: what example do you have at the beginning at which you could observe and know that that is the case or what is the novel predictions from an indirect observation basis at which you can make that conclusion
Reply: B.Alberts: Molecular Biology of the Cell. 4th edition.
If left uncorrected when the DNA is replicated, most of these changes would be expected to lead either to the deletion of one or more base pairs or to a base-pair substitution in the daughter DNA chain. ( see below ) The mutations would then be propagated throughout subsequent cell generations. Such a high rate of random changes in the DNA sequence would have disastrous consequences for an organism
https://www.ncbi.nlm.nih.gov/books/NBK26879/

PHILIP HEMME: Nobel Prize in Chemistry 2015: DNA Repairing Mechanisms that Keep you Alive 07/10/2015
The 2015 Nobel Prize in Chemistry has been awarded to three scientists for their truly amazing discoveries about the DNA code of life. An article from the Swedish Academy of Science highlights the significance of these discoveries for understanding how our cells can copy the DNA code millions of times with hardly ever making a mistake. 1 ( See article 32 )
DNA repair mechanisms are crucial to our existence. Without them, we would not survive because of DNA damage caused by the environment (e.g UV light damage, radiation etc.)
https://www.labiotech.eu/trends-news/nobel-prize-2015-dna-repairing-mechanism-keeps-alive-rewarded/

JMike: like catalytic functions of uh ribozymes or anything like that
Reply: The origin of replication and translation and the RNA World
https://reasonandscience.catsboard.com/t2234-the-origin-of-replication-and-translation-and-the-rna-world

The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.
https://en.wikipedia.org/wiki/RNA_world

Leslie Orgel: Prebiotic chemistry and the origin of the RNA world Mar-Apr 2004
It is possible that all of these, and many other difficulties, will one day be overcome and that a convincing prebiotic synthesis of RNA will become available. However, many researchers in the field, myself included, think that this is unlikely
https://pubmed.ncbi.nlm.nih.gov/15217990/

Christian de Duve: The Beginnings of Life on Earth September-October 1995 issue of American Scientist.
Contrary to what is sometimes intimated, the idea of a few RNA molecules coming together by some chance combination of circumstances and henceforth being reproduced and amplified by replication simply is not tenable. There could be no replication without a robust chemical underpinning continuing to provide the necessary materials and energy.
https://www2.nau.edu/~gaud/bio372/class/readings/beglifeerth.htm

Robert Shapiro: Small Molecule Interactions were Central to the Origin of Life (June 2006),
The myth of a small RNA molecule that arises de novo and can replicate efficiently and with high fidelity under plausible prebiotic conditions . . . [is] unrealistic in light of current understanding of prebiotic chemistry
https://www.jstor.org/stable/10.1086/506024

JMike: or polymerizing on hot clay like you would disagree with that or is that is that
Reply: RNA & DNA: It's prebiotic synthesis: Impossible !!
https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible#6847

Robert Shapiro Do natural clays catalyze this reaction? June 2006
The attractiveness of this oligonucleotide synthesis rests in part in the ready availability of the catalyst. Montmorillonite is a layered clay mineral-rich in silicate and aluminum oxide bonds. It is widely distributed in deposits on the contemporary Earth. If the polymerization of RNA subunits was a common property of this native mineral, the case for RNA at the start of life would be greatly enhanced.
However, the “[c]atalytic activity of native montmorillonites before being converted to their homoionic forms is very poor” (Ertem 2004:567). The native clays contain bound polyvalent cations, such as Cu2, Fe3, and Zn2, that interfere with phosphorylation reactions. This handicap was overcome in the synthetic experiments by titrating the clays to a monoionic form, generally sodium, before they were used. Even after this step, the activity of the montmorillonite depended strongly on its physical source, with samples from Wyoming yielding the best results (Ferris et al. 1989; Ertem 2004). Eventually the experimenters settled on Volclay, a commercially processed Wyoming montmorillonite provided by the American Colloid Company. Further purification steps were applied to obtain the catalyst used for the “prebiotic” formation of RNA.
https://www.jstor.org/stable/10.1086/506024

JMike: you know it seems like if we took like a meme of it it's like they're working in a lab and you're on your phone like on the toilet researching things you know what i mean it seems to just seems to be you're assuming things that other models don't agree with
Reply: The Lab experiments warrant the conclusion that abiogenesis is not possible.

Abiogenesis is mathematically impossible
https://reasonandscience.catsboard.com/t1279-abiogenesis-is-mathematically-impossible

Jack W. Szostak: It is virtually impossible to imagine how a cell’s machines, which are mostly protein-based catalysts called enzymes, could have formed spontaneously as life first arose from nonliving matter around 3.7 billion years ago.
https://www.mrgscience.com/uploads/2/0/7/9/20796234/origin_of_life_sci_am.pdf

Eugene V. Koonin: The Logic of Chance: page 252:
" Despite many interesting results to its credit, when judged by the straightforward criterion of reaching (or even approaching) the ultimate goal, the origin of life field is a failure—we still do not have even a plausible coherent model, let alone a validated scenario, for the emergence of life on Earth.

Steve Benner: Paradoxes in the origin of life
Discussed here is an alternative approach to guide research into the origins of life, one that focuses on “paradoxes”, pairs of statements, both grounded in theory and observation, that (taken
together) suggest that the “origins problem” cannot be solved.

Graham Cairns-Smith: Genetic takeover, page 66:
Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis.

Garrett: Biochemistry, 6th ed, page 665
Key compounds, such as arginine, lysine, and histidine; the straight-chain fatty acids; porphyrins; and essential coenzymes, have not been convincingly synthesized under simulated prebiotic conditions.

Robert Shapiro: A Replicator Was Not Involved in the Origin of Life
A profound difficulty exists, however, with the idea of RNA, or any other replicator, at the start of life. Existing replicators can serve as templates for the synthesis of additional copies of themselves, but this device cannot be used for the preparation of the very first such molecule, which must arise spontaneously from an unorganized mixture. The formation of an information-bearing homopolymer through undirected chemical synthesis appears very improbable.

Question: Let's suppose you see a machine made for specific functions. And you see nearby another machine, that is set up constantly to monitor the function of the first machine, and knows when it performs properly, and when an error occurs. And then, when something goes havoc, that machine knows immediately what error occurred, and has the know-how to fix it. Is it more rational to infer that intelligence was required to set up both machines, or rather that both are the product of random unguided events?

1. Organisms are constantly exposed to different environments, and in order to survive, require to be able to adapt to external conditions.
2. Life, in order to perpetuate, has to replicate. That includes DNA, which must be replicated with extreme accuracy. Somehow, the cell knows when DNA is accurately replicated, and when not. There are extremely complex quality control mechanisms in place, which constantly monitor the process. At least 3 error check and repair mechanisms keep error during replication down to 1 error in 10 billion nucleotides replicated.
3. These repair mechanisms, sophisticated proteins, are also encoded in DNA. So proteins are required to error check and repair DNA but accurately replicated DNA is necessary to make the proteins that repair DNA.
4. That is an all-or-nothing business. Therefore, these sophisticated systems had to emerge all at once, and require a designer.

1. The origin of life, and perpetuation of life, depends on the accurate replication of DNA. At least 3 error check and repair mechanisms keep error during replication down to 1 error in 10 billion nucleotides replicated.
2. That depends on very sophisticated error check and repair proteins, which had to be in operation from day one.
3. Instructions in DNA are required to make error check and repair proteins, but these proteins have to be there from day one to error check and repair DNA. That is an all or nothing business.
4. The complexity of the first living cell had to be set up fully formed right from the beginning, and that requires intelligence.

DNA and RNA error checking and repair, amazing evidence of design
https://reasonandscience.catsboard.com/t2043-dna-and-rna-error-checking-and-repair-amazing-evidence-of-design

Error check and repair mechanisms require foresight
https://reasonandscience.catsboard.com/t3105-error-check-and-repair-mechanisms-require-foresight

Error detection and repair during the biogenesis & maturation of the ribosome, tRNA's, Aminoacyl-tRNA synthetases, and translation: by chance, or design?
https://reasonandscience.catsboard.com/t2984-error-check-and-repair-during-messengerrna-translation-in-the-ribosome-by-chance-or-design

Otangelo

Otangelo

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How do molecular motors convert chemical energy in to mechanical work? August 25, 2022

https://www.sciencedaily.com/releases/2022/08/220825120337.htm

Molecular motors are complex devices composed of many different parts that consume energy to perform various cellular activities. In short, molecular machines transform energy into useful work. Understanding the mechanistical aspects underlying these motors begins with generating a detailed description of their overall architecture and atomic organisation. However, to uncover the core mechanisms energizing these motors it is essential to decode all of the molecular dynamics in atomic detail.

Now, the research team of Thomas C. Marlovits from the Centre for Structural Systems Biology CSSB at DESY and the University Medical Center Hamburg-Eppendorf (UKE) in Hamburg reveals the architecture, complete functional cycle and the mechanism of such a molecular motor: They report in the journal Nature, how a 'RuvAB branch migration complex' converts chemical energy into mechanical work to perform recombination and repair of DNA.

DNA recombination is one of the most fundamental biological processes in living organisms. It is the process by which chromosomes "swap" DNA either to generate genetic diversity, by creating new offspring, or to maintain genetic integrity, by repairing breaks in existing chromosomes. During DNA recombination, four DNA arms separate from their double-helix formations and join together at an intersection known as a Holliday junction. Here the DNA arms exchange strands in a process called active branch migration.

The essential energy needed for this branch migration to occur comes from a molecular machinery that scientists have tagged as the RuvAB branch migration complex. This complex assembles around the Holliday junction and is made of two motors labelled RuvB AAA+ ATPases, that fuel the reaction, and a RuvA stator. The research team has now provided an intricate blueprint that explains how the RuvB AAA+ motors work under the regulation of the RuvA protein to perform synchronized DNA movement.

The active branch migrations energized by the RuvB AAA+ motor molecule are very fast and highly dynamic. To determine the individual steps of this process, the scientists used time-resolved cryo electron microscopy to observe the motor's machinery in slow motion. "We basically provided the RuvB AAA+ motor with a slower burning fuel which allowed us to capture the biochemical reactions as they occur," explains Marlovits.

The scientist captured over ten million images of the motor machinery interacting with the Holliday junction. Jiri Wald (CSSB, UKE and part of the Vienna BioCenter PhD Program), the paper's first author, combed through the immense amount of data and carefully classified the subtle changes occurring in each image. Using the high-performance computing facility at DESY, the scientists were then able to put all the puzzle pieces together to generate a high-resolution movie detailing how the RuvAB complex functions on the molecular scale.

"We were able to visualize seven distinct states of the motor and demonstrate how the interconnected elements work together in a cyclical manner," explains Wald. "We also demonstrated that the RuvB motor converts energy into a lever motion which generates the force that drives branch migration. We were amazed by the discovery that the motors use a basic lever mechanism to move the DNA substrate. Overall, the sequential mechanism, coordination and force generation manner of the RuvAB motor share conceptual similarities with combustion engines."

AAA+ motors are often used in other biological systems, such as protein transport, therefore this detailed model of the RuvB AAA+ motor can be used as a blueprint for similar molecular motors. "We understand how the motor works and now we can put this motor into another system with some minor adaptations," explains Marlovits. "We are essentially presenting core principles for AAA+ motors."

The Marlovits group's future work will explore ways to interfere with the function of AAA+ motors. This could provide the basis for the development of a new generation of drugs, which would disrupt the mechanisms of such a motor in pathogens and thus halt the spread of infection. "We are excited to explore the possibilities that exist now that we have a blueprint of the RuvB AAA+ motor," notes Wald.

Scientists from CSSB, UKE, the Institute of Molecular Biotechnology, the Research Institute of Molecular Pathology, both in Vienna, Austria, and DESY contributed to this research.

CSSB is a joint initiative of ten research partners from Northern Germany, including three universities and six research institutes that devotes itself to infection biology research.

DESY is one of the world's leading particle accelerator centres and investigates the structure and function of matter -- from the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the universe. The particle accelerators and detectors that DESY develops and builds at its locations in Hamburg and Zeuthen are unique research tools. They generate the most intense X-ray radiation in the world, accelerate particles to record energies and open up new windows onto the universe. DESY is a member of the Helmholtz Association, Germany's largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the German federal states of Hamburg and Brandenburg (10 per cent).

Otangelo

Otangelo

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In Cells, Proofreading and Repair Testify to Intelligent Design and Foresight
https://evolutionnews.org/2020/09/in-cells-proofreading-and-repair-testify-to-intelligent-design-and-foresight/

The concepts of machine and factory error monitoring, checking, and repair are all tasks performed with goal-directedness, intent, and purpose.
1. Repairing things that are broken, malfunctioning, or instantiating complex systems that autonomously prevent things to break are always actions performed by agents with intentions, volition, goal-orientedness, foresight, understanding, and know-how.
2. Man-made machines almost always require direct intelligent intervention by technicians to recognize errors, find which parts of a machine are broken, know how to remove and replace them without breaking surrounding parts of the device, and know how to construct the part that has to be replaced with fidelity, and re-insert and re-connect it where the part was removed. The entire process is complex, demanding know-how, and depends on a high quantity of intelligence in performing all involved actions.
3. Man has not been able to create a fully autonomous, preprogrammed machine or factory, that is able to quality and error monitor all manufacturing processes and the correct performance of all devices involved, and if the products are up to the required quality standard, and, if something drives havoc, repair and re-establish normal function of what was broken or malfunctioning without external intervention.
4. C.H. Loch writes in the science paper: "Organic Production Systems: What the Biological Cell Can Teach Us About Manufacturing" (2004): Biological cells are preprogrammed to use quality-management techniques used in manufacturing today. The cell invests in defect prevention at various stages of its replication process, using 100% inspection processes, quality assurance procedures, and foolproofing techniques. An example of the cell inspecting each and every part of a product is DNA proofreading. As the DNA gets replicated, the enzyme DNA polymerase adds new nucleotides to the growing DNA strand, limiting the number of errors by removing incorrectly incorporated nucleotides with a proofreading function. Following is an impressive example: Unbroken DNA conducts electricity, while an error blocks the current. Some repair enzymes exploit this. One pair of enzymes lock onto different parts of a DNA strand. One of them sends an electron down the strand. If the DNA is unbroken, the electron reaches the other enzyme and causes it to detach. I.e. this process scans the region of DNA between them, and if it’s clean, there is no need for repairs. But if there is a break, the electron doesn’t reach the second enzyme. This enzyme then moves along the strand until it reaches the error, and fixes it. This mechanism of repair seems to be present in all living things, from bacteria to man. Know-how is needed:

a. To know that something is broken (DNA damage sensing)
b. To identify where exactly it is broken
c. To know when to repair it (e.g. one has to stop/or put on hold some other ongoing processes, in other words, one needs to know lots of other things, one needs to know the whole system, otherwise one creates more damage…) d. to know how to repair it (to use the right tools, materials, energy, etc, etc, etc )
e. to make sure that the repair was performed correctly. (this can be observed in DNA repair as well)

5. On top of that: Cells do not even wait until a protein machine fails, but replace it long before it has a chance to break down. Furthermore, it completely recycles the machine that is taken out of production. The components derived from this recycling process can be used not only to create other machines of the same type but also to create different machines if that is what is needed in the “plant.” This way of handling its machines has some clear advantages for the cell. New capacity can be installed quickly to meet current demand. At the same time, there are never idle machines around taking up space or hogging important building blocks. Maintenance is a positive “side effect” of the continuous machine renewal process, thereby guaranteeing the quality of output. Finally, the ability to quickly build new production lines from scratch has allowed the cell to take advantage of a big library of contingency plans in its DNA that allow it to quickly react to a wide range of circumstances, as we will describe next.
6. The more sophisticated, advanced, autonomous, complex, and information-driven machines or factories are, the more they carry the hallmark of design. The very concepts of error monitoring, checking, and repair, and replacement in advance to avoid future break-ups are tasks performed with goal-directedness, and purpose. Biological cells are far more advanced than any machine and factory ever devised and invented by man. It is therefore rational and warranted to infer, that biological cells were designed.

1. Mechanisms of Hair Cell Damage and Repair: Hair cells acquire damage from a variety of environmental and genetic factors. To fully maintain auditory function, damaged hair cells must be repaired.

1. Elizabeth L.Wagner: Mechanisms of Hair Cell Damage and Repair 6, June 2019: https://www.sciencedirect.com/science/article/abs/pii/S0166223619300402

Last edited by Otangelo on Sat Oct 29, 2022 1:19 pm; edited 1 time in total

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Error checking and repair systems in the cell, amazing evidence of design

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