elife-64592-v2.pdf (5.41 MB)
CDK control pathways integrate cell size and ploidy information to control cell division.
journal contributionposted on 2021-07-21, 13:43 authored by James Oliver Patterson, Souradeep Basu, Paul Rees, Paul Nurse
Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth, and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell-size homeostasis.
Crick (Grant ID: 10121, Grant title: Nurse FC001121) Wellcome Trust (Grant ID: 214183/Z/18/Z, Grant title: WT 214183/Z/18/Z) Wellcome Trust (Grant ID: 093917/C/10/A, Grant title: WT 093917/C/10/A)