A functional skeletal system requires the COORDINATED DEVELOPMENT of many different tissue types, including cartilage, bones, joints, and tendons. 1
Interdependency and phosphorylation of KIF4 and condensin I are essential for organization of chromosome scaffold
17 Aug 2017
Kinesin family member 4 (KIF4) and condensins I and II are essential chromosomal proteins for chromosome organization by locating primarily to the chromosome scaffold. However, the mechanism of how KIF4 and condensins localize to the chromosome scaffold is poorly understood. Here, we demonstrate a close relationship between the chromosome localization of KIF4 and condensin I, but not condensin II, and show that KIF4 and condensin I assist each other for stable scaffold formation by forming a stable complex. Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo-like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome. Aurora B activity facilitates the targeting of KIF4 and condensin I to the chromosome, whereas Plk1 activity promotes the dissociation of these proteins from the chromosome. Thus, the interdependency between KIF4 and condensin I, and their phosphorylation states play important roles in chromosome scaffold organization during mitosis.
In this study, we further examined the interdependency of KIF4 and other scaffold proteins in chromosome organization. The results reveal that KIF4 localization to the chromosome scaffold is regulated interdependently with condensin I. The results indicate an interdependency of localization of KIF4 and condensin I on the chromosome scaffold.
It has been shown that condensin I loading to the chromosome is largely regulated by Aurora B [22–25]. This modification of condensin I is found to be conserved from yeast to humans . Interdependency and physical interaction between KIF4 and condensin I for their chromosome localization raise the question whether KIF4 is regulated by Aurora B. In this study, interdependency and physical interaction between KIF4 and condensin I for localization to the chromosome were revealed. These results suggest that the interaction between KIF4 and condensin I may assist both proteins to bind and organize stably to the chromosome scaffold.
Scott Minnich at U. Idaho sends this along:
This paper published online his summer is a true mind-blower showing the irreducible organizational complexity (author’s description) of DNA analog and digital information, that genes are not arbitrarily positioned on the chromosome etc.
The paper by Muskhelishvili and Travers, titled “Integration of syntactic and semantic properties of the DNA code reveals chromosomes as thermodynamic machines converting energy into information”, makes several very interesting points. First, the digital information of individual genes (semantics) is dependent on the the intergenic regions (as we know) which is like analog information (syntax). Both types of information are co-dependent and self-referential but you can’t get syntax from semantics. As the authors state, “thus the holistic approach assumes self-referentiality (completeness of the contained information and full consistency of the the different codes) as an irreducible organizational complexity of the genetic regulation system of any cell”. In short, the linear DNA sequence contains both types of information. Second, the paper links local DNA structure, to domains, to the overall chromosome configuration as a dynamic system keying off the metabolic signals of the cell. This implies that the position and organization of genes on the chromosome is not arbitrary—much like Karl Drlica proposed years ago as we were obtaining the first bacterial genome sequences. In other words, DNA topology (due to supercoiling and histone-like protein binding), Transcription, and Metabolic energy (ATP levels influence DNA gyrase activity, which affects supercoiling, which affects transcription) are all keying off each other and thus there is an overall order to the positioning of anabolic and catabolic genes relative to the origin of replication. In short, I think this is a fascinating review looking at DNA organization and function which, in the authors words, are irreducibly complex.
Understanding genetic regulation is a problem of fundamental importance. Recent studies have made it increasingly evident that, whereas the cellular genetic regulation system embodies multiple disparate elements engaged in numerous interactions, the central issue is the genuine function of the DNA molecule as information carrier. Compelling evidence suggests that the DNA, in addition to the digital information of the linear genetic code (the semantics), encodes equally important continuous, or analog, information that specifies the structural dynamics and configuration (the syntax) of the polymer. These two DNA information types are intrinsically coupled in the primary sequence organisation, and this coupling is directly relevant to regulation of the genetic function. In this review, we emphasise the critical need of holistic integration of the DNA information as a prerequisite for understanding the organisational complexity of the genetic regulation system.
Last edited by Admin on Tue Nov 13, 2018 12:18 pm; edited 4 times in total