Chromatin re-organisation at the transition from mitosis to G1: how phospho- switches regulate the process in space and time (360G-Wellcome-210742_Z_18_Z)

Reversible protein phosphorylation is the most used regulatory mechanism adopted by cells and cell division (mitosis) heavily relies on this. Protein phosphatases are inactivated at the beginning of mitosis and must be re- activated at its end to produce viable products. My study will focus on Protein Phosphatase1 (PP1) complexes: Repo-Man/PP1, PNUTS/PP1 and Ki-67/PP1. This choice has been made based on studies conducted in my laboratory where we have identified the complexes important for nuclear structure and chromatin organisation in mitosis. The aim of this investigation is to provide the first integrated picture of the role of PP1 at the Mitosis-G1 transition, thereby filling crucial knowledge gaps in the field of mitotic exit. By combining genetic, biochemistry and cell biology, I will identify the main substrates of these complexes during mitotic exit, how they modify chromatin architecture and their mitotic and non-mitotic roles. The data obtained from this project will generate essential information on the G1 nucleus re-establishment network. The identification of substrates, their de-phosphorylation order and biological consequences, will pave the path towards modeling the cascade of events that drive mitotic exit execution and explain how cellular homeostasis is maintained.