A novel control mechanism of mitotic exit in Saccharomyces cerevisiae

Mitotic exit is the cell cycle stage in which the cell transits from M phase to a new G1 phase. While mitosis is under control of cyclin-dependent kinases (CDK), mitotic exit depends on inactivation of CDKs. Timely coordination of mitotic CDK inactivation with respect to chromosome segregation is important to avoid aneuploidy and maintain ploidy. A comprehensive understanding of regulation of mitotic exit is missing. In budding yeast, mitotic exit is achieved by the use of a special network, called Mitotic Exit Network. An inhibitor to Mitotic Exit Network, Kin4 kinase, leads to lethality for the cells when is expressed in high doses. Our goal is to find out novel mechanisms of mitotic exit control. In this thesis, we identified a temperature sensitive mutant that rescues the lethality of Kin4 overexpression. Through a "dosage suppressive genetic screening", we found two genes, SAN1 and PHO2, that retarded growth this temperature sensitive mutant when Kin4 was overexpressed. We further characterized the effect of these genes on mitotic exit, with a focus on SAN1. Our results indicate a novel regulatory mechanism for mitotic exit. Data presented in this thesis will pave the way to illuminate a new section in the process of exiting from mitosis. Owing to the fact that the basic cellular tasks are preserved from yeast to human, we envisage that characterization of this newly emerged role in the mitotic exit of S. cerevisiae would contribute to the understanding of analogous control mechanisms in more complex organisms.