Differential contribution of the chromatin-associated PP1 binding proteins PNUTS, Repo-Man and Ki-67 to mitotic exit and G1 re-establishment.
Mitotic exit is an important part of the cell cycle that requires coordination of many chromatin and cytoskeleton remodelling events to successfully complete cell division and maintain cell identity. Protein de-phosphorylation is a key step in directing mitotic exit and protein phosphatase 1 (PP1) is essential to this process. However, the specific contribution of its numerous targeting subunits is still unknown. Here we have investigated the function of three chromatin-associated PP1 targeting subunits in exiting mitosis: Repo-Man, Ki-67 and PNUTS. We have generated endogenously tagged, auxin-degradable alleles for each subunit and used a multi-omic approach to address their specific contribution to transcription resumption, chromatin accessibility and protein phosphorylation at the transition from mitosis to G1. This approach has identified their distinct role in mitotic exit, provided unique datasets for the cell cycle community, and highlighted specific and novel functions for Ki-67 and Repo-Man in genome stability and organisation.