Mechanisms for maintaining genomic integrity during chromosome segregation in budding yeast

Abstract

Maintaining genomic integrity is crucial for an organism's fitness and survival. Regulation of chromosome segregation requires complex surveillance mechanisms that vary for different loci within the genome. This thesis focuses on two complexes, monopolin (made up of Lrs4, Csml and Maml) and condensin, a protein complex required for chromosome condensation, and their roles in chromosome segregation during mitosis and meiosis. During mitosis, Lrs4-Csml and condensiin reside in the nucleolus where they regulate the maintenance and segregation of the budding yeast ribosomal DNA array, a highly repetitive and transcriptionally active locus. Here I show that Lrs4 and Csml bind the RENT complex at the non-transcribed space region 1 within the rDNA array and via cohesin or condensin inhibit unequal exchange between sister chromatids. This complex is released during anaphase, during which Lrs4 and Csml localize to kinetochores, where they play a role in mitotic chromosome segregation. Although their role in meiotic chromosome Here we show that Lrs4 and Csml collaborate with condensins at kinetochores to control mitotic and meiotic chromosome segregation. During meiosis, diploid cells must first segregate homologous chromosomes before sister chromatids can separate. Lrs4-Csml and condensin are required during the first meiotic division to bring about the co-segregation of sister chromatids towards one pole and for the binding of monopolin subunit Maml. In summary, I show here that condensins and Lrs4-Csml are required at various chromosomal locations to provide linkages between sister chromatids to promote high fidelity chromosome segregation.