Mitosis exit regulation by cdc5 and pp2a-cdc55

Resumen

Cell cycle progression is regulated by different mechanisms which are mostly dependent on kinases and phosphatases action. Clb2-Cdc28 is the major cyclin-Cdk complex controlling mitosis in budding yeast. Clb2-Cdc28 activity peaks at metaphase and is inactivated to exit from mitosis mostly by the Cdc14 mitotic phosphatase. Two pathways contribute to Cdc14 activation: FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network). Clb2-Cdk1 dependent Net1 phosphorylation provokes the FEAR-Cdc14 activation. However, it is not the unique kinase contributing to mitosis. Polo-like kinase Cdc5 was also described to be involved in the regulation of Cdc14. Cdc5 function in mitotic exit and Cdc14 activation requires sequential activation by Clb2-Cdk1. Nevertheless, the in vivo Net1 phosphorylation sites phosphorylated by Cdc5 have not been described, obscuring the Cdc5 role in the Cdc14 activation. Here, we described the Cdc5 involvement in the Net1 phosphorylation by the identification of some Cdc5-dependent phosphorylation sites on Net1. On the other hand, phosphatases also contribute to the regulation of mitosis. Cdc14 triggers mitosis exit and cytokinesis; while PP2ACdc55 has several functions during mitosis. In this thesis we described the new PP2ACdc55 role in cytokinesis. We demonstrated that PP2ACdc55 dephosphorylates pivotal proteins for proper cytokinesis completion and their deregulation promote defects during cytokinesis. Taking all together, this thesis contributes to the knowledge of the kinases and phosphatases roles during mitosis and cytokinesis.