Novel mechanisms in control of mitotic exit

Mitotic exit network is a G-protein signaling process that regulates the exit from mitosis. This process must be tightly regulated for proper cell division. The aim of this thesis is to characterize novel mechanisms controlling mitotic exit. For this purpose, two independent but related mechanisms are studied in Saccharomyces cerevisiae, budding yeast. The first mechanism focuses on an unanticipated effect of the daughter cortex localized bud site selection protein Bud14 on Cdc14 which is the main protein phosphatase that triggers the mitotic exit in budding yeast. Our data shows that in the absence of BUD14 or if Bud14 cannot bind to the protein phosphatase 1 (bud14-F379A), Cdc14 stays longer at the spindle pole body (SPB). SPB localization of Cdc14 was dependent on the Cdc14 release mechanisms FEAR and MEN as well as the mitotic exit inhibitor protein Bfa1. Thus, Bud14-Glc7 is part of the mechanism that controls Cdc14 localization to SPBs. The second part of the thesis investigates the mechanisms by which Cdc36 influences mitotic exit. Cdc36 is a component involved in CCR4-NOT complex which have roles in a variety of mechanisms in mRNA regulation and translation. Our data show, cdc36-16 mutant rescues a mitotic exit defective yeast strain. We performed RNAseq analysis of WT and cdc36-16 cells during their synchronous progression in the cell cycle from anaphase onset until mitotic exit. Many cell cycle related genes were found to be differentially regulated in cdc36-16. Our data thus suggest Cdc36 dependent expression is important for a timely mitotic exit. Taken together, in this thesis, we discovered novel conserved proteins (Bud14-Glc7 and Cdc36) that take part in mitotic exit control. We anticipate that these conserved proteins may have similar functions in higher eukaryotes.