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CDK control pathways integrate cell size and ploidy information to control cell division

James Oliver Patterson, Souradeep Basu, Paul Rees Orcid Logo, Paul Nurse

eLife, Volume: 10

Swansea University Author: Paul Rees Orcid Logo

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DOI (Published version): 10.7554/elife.64592

Abstract

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...

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Published in: eLife
ISSN: 2050-084X
Published: eLife Sciences Publications, Ltd 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa57132
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Abstract: 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.
College: College of Engineering
Funders: We thank Jessica Greenwood and Clovis Basier for their extensive efforts in editing the manuscript. This work was supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (FC01121), the UK Medical Research Council (FC01121), and the Wellcome Trust (FC01121). In addition, this work was supported by the Wellcome Trust Grant to PN (grant number 214183 and 093917), The Lord Leonard and Lady Estelle Wolfson Foundation, and Woosnam Foundation. JOP and PR acknowledge the support of the Biotechnology and Biological Sciences Research Council under grant BB/P026818/1. PR also acknowledges the support of the Biotechnology and Biological Sciences Research Council/National Science Foundation under grant BB/N005163/1 and NSF DBI 1458626. JOP acknowledges support from the Boehringer Ingelheim Fonds PhD fellowship.