Redundancy and Specialisation of Cyclin Dependent Kinases

ABSTRACT: Cyclin dependent kinases (CDKs) lie at the heart of eukaryotic cell division, with different CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs)1-3. However, the principles on which cyclin-CDKs organise the cell cycle are still contentious, with current theories suggesting that either M-CDKs and S-CDKs are redundant with each other, and simply serve as a source of CDK activity, or that they are functionally specialised and execute distinct tasks. Here we reconcile these two views, showing that although S-CDKs are unable to drive mitosis, global CDK phosphorylation in vivo between S-CDK and M-CDK is surprisingly similar. Remarkably, S-CDK has cryptic mitotic activity which can be exposed by the removal of Protein Phosphatase 1 (PP1). In particular, removal of centrosomal PP1 allows S-CDK to execute mitosis indistinguishably from M-CDK, demonstrating their functional redundancy. Thus, we reconcile the two opposing views of cell cycle control, showing that although there is a minor level of specialisation between S-CDKs and M-CDKs, that the core cell cycle engine is based upon modulation of CDK activity, with cyclins providing refinements to this core system.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Schizosaccharomyces Pombe 972h-

SUBMITTER: Andrew Jones  

LAB HEAD: Paul Nurse

PROVIDER: PXD029073 | Pride | 2022-03-22

REPOSITORIES: Pride