Regulation of centromere function by R37 methylation and K49 acetylation of CENP-A/ Cse4 in Saccharomyces cerevisiae

Centromeres of eukaryotic chromosomes mark the site for kinetochore formation and microtubule attachment and are essential for accurate chromosome segregation. Centromere identity is defined by the presence of the histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae). In this project, we will elucidate the function and interplay of two posttranslational modifications on Cse4 from the yeast S. cerevisiae that we have identified. We have previously reported arginine methylation of Cse4, and we have furthermore identified a novel acetylation site modification. This proposal will aim at identifying the molecular basis for how these modifications mechanistically regulate kinetochore assembly, thus generating molecular knowledge of the regulation of kinetochore assembly and chromosome segregation by posttranslational modification of CENP-A/ Cse4. It thus opens up a new avenue of research into the molecular “interpretation” of PTMs on the centromeric histone variant CENP-A.