Organisation of pericentromeric chromatin in Saccharomyces cerevisiae (360G-Wellcome-109091_Z_15_A)

Successful cell division relies on faithful chromosome segregation. Central to this process is sister chromatid cohesion by cohesin that topologically entraps sister chromatids. Cohesin shows increased association with chromosomal regions surrounding the centromere, called pericentromeres. Pericentromeric cohesin is crucial during both meiosis and mitosis. In meiosis I, when homologous chromosomes segregate, pericentromeric cohesion is protected from separase-dependent cleavage ensuring that sister chromatids stay together until they segregate in meiosis II. In mitosis and meiosis II, pericentromeric cohesin facilitates chromosome biorientation by establishing preferred kinetochore geometry for capture by microtubules. How exactly pericentromeric cohesion facilitates chromosome biorientation is unknown. It was proposed that pericentromeric cohesin establishes intramolecular linkages allowing the pericentromere to adopt a cruciform structure. This would facilitate a back-to-back geometry of kinetochores and would promote kinetochore capture by microtubules from opposite spindle poles. This project aims to characterise the conformation of the pericentromere in budding yeast. I will examine how the conformation of pericentromeric chromatin responds to the presence and absence of tension that is exerted on chromosomes during biorientation. The research will extend to mitotic and meiotic cells, with wild type and cohesin-deficient backgrounds. Ultimately, this will further our understanding on how kinetochore geometry facilitates accurate chromosome segregation.