CDK control pathways integrate cell size and ploidy information to control cell division
- The Francis Crick Institute, United Kingdom
- Swansea University, United Kingdom
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.
Data availability
Analysed data has been uploaded to Figshare with the handle 10779/crick.14633037.
Article and author information
Author details
James Oliver Patterson
Funding
Boehringer Ingelheim Fonds
- James Oliver Patterson
Cancer Research UK (FC01121)
- James Oliver Patterson
- Souradeep Basu
- Paul Nurse
Medical Research Council (FC01121)
- James Oliver Patterson
- Souradeep Basu
- Paul Nurse
Wellcome Trust (FC01121)
- James Oliver Patterson
- Paul Rees
- Paul Nurse
Wellcome Trust (214183)
- James Oliver Patterson
- Souradeep Basu
- Paul Nurse
The Lord Leonard and Lady Estelle Wolfson Foundation
- James Oliver Patterson
- Souradeep Basu
- Paul Nurse
Biotechnology and Biological Sciences Research Council (BB/P026818/1)
- James Oliver Patterson
- Paul Rees
Biotechnology and Biological Sciences Research Council (BB/N005163/1)
- Paul Rees
National Science Foundation (1458626)
- Paul Rees
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Patterson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,307
- views
-
- 538
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Citations by DOI
-
- 26
- citations for umbrella DOI https://doi.org/10.7554/eLife.64592
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
CDK control pathways integrate cell size and ploidy information to control cell division
eLife 10:e64592.
https://doi.org/10.7554/eLife.64592
