Unravelling Centromeric evolution by Nucleosome elasticity

Authors

• J Kolay
• DP Melters
• M Bui
• Y Dalal

Abstract

Faithful chromosome segregation, which is indispensable for survival of all organisms, is evolutionarily conserved across most eukaryotes. Despite the function being preserved, both centromeric DNA and kinetochore proteins are rapidly evolving. These contrasting aspects of centromere biology are known as “centromere paradox”. This motivates us to understand mechanistic basis of centromeric evolution. Unlike canonical histone proteins which are nearly invariant through evolution, centromeres are epigenetically defined by fast-evolving histone H3 variant CENP-A. Recently we reported that CENP-A nucleosomes are two-fold more elastic than canonical H3 nucleosomes, and get stiffer when bound to essential kinetochore protein CENP-C. In this work, we investigate whether CENP-A elasticity is a conserved feature across eukaryotes and co-evolves with kinetochore proteins. To study nucleosome elasticity in different eukaryotic models, we selected CENP-A from Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. Preliminary results indicate that human CENP-A nucleosomes are the most elastic followed by canonical H3, budding yeast Cse4 and Arabidopsis CenH3 nucleosomes. Although the size of human centromere tandem repeat (171 bp) is in same range as that of Arabidopsis with 178 bp in length, there is no resemblance in elasticity between human CENP-A and Arabidopsis CenH3. Whereas budding yeast point centromere is 125 bp in size with AT rich CDEII DNA elements. Therefore, considering genetic diversity of centromeres, CENP-A elasticity may be centromere specific and not a conserved feature among eukaryotes. To expand this study further, we have chosen H3.3 glioblastoma mutants to understand relationship between cancer mutations and mechanical characteristics at single nucleosome level.

Scientific Focus Area: Chromosome Biology

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