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

  1. James Oliver Patterson  Is a corresponding author
  2. Souradeep Basu  Is a corresponding author
  3. Paul Rees
  4. Paul Nurse
  1. The Francis Crick Institute, United Kingdom
  2. 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.

The following data sets were generated

Article and author information

Author details

  1. James Oliver Patterson

    Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    jamesop@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1993-4500
  2. Souradeep Basu

    Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom
    For correspondence
    saz.basu@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4448-8688
  3. Paul Rees

    College of Engineering, Swansea University, Swansea, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Paul Nurse

    Cell Cycle Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

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.

Reviewing Editor

  1. Silke Hauf, Virginia Tech, United States

Version history

  1. Received: November 4, 2020
  2. Accepted: May 24, 2021
  3. Accepted Manuscript published: June 11, 2021 (version 1)
  4. Version of Record published: July 1, 2021 (version 2)

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.

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  1. James Oliver Patterson
  2. Souradeep Basu
  3. Paul Rees
  4. Paul Nurse
(2021)
CDK control pathways integrate cell size and ploidy information to control cell division
eLife 10:e64592.
https://doi.org/10.7554/eLife.64592

Share this article

https://doi.org/10.7554/eLife.64592

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