Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast

Daniel Keifenheim, Xi Ming Sun, Edridge D'Souza, Makoto J. Ohira, Mira Magner, Michael B. Mayhew, Samuel Marguerat, Nicholas Rhind

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Proper cell size is essential for cellular function. Nonetheless, despite more than 100 years of work on the subject, the mechanisms that maintain cell-size homeostasis are largely mysterious [1]. Cells in growing populations maintain cell size within a narrow range by coordinating growth and division. Bacterial and eukaryotic cells both demonstrate homeostatic size control, which maintains population-level variation in cell size within a certain range and returns the population average to that range if it is perturbed [1, 2]. Recent work has proposed two different strategies for size control: budding yeast has been proposed to use an inhibitor-dilution strategy to regulate size at the G1/S transition [3], whereas bacteria appear to use an adder strategy, in which a fixed amount of growth each generation causes cell size to converge on a stable average [4–6]. Here we present evidence that cell size in the fission yeast Schizosaccharomyces pombe is regulated by a third strategy: the size-dependent expression of the mitotic activator Cdc25. cdc25 transcript levels are regulated such that smaller cells express less Cdc25 and larger cells express more Cdc25, creating an increasing concentration of Cdc25 as cells grow and providing a mechanism for cells to trigger cell division when they reach a threshold concentration of Cdc25. Because regulation of mitotic entry by Cdc25 is well conserved, this mechanism may provide a widespread solution to the problem of size control in eukaryotes.

Original languageEnglish (US)
Pages (from-to)1491-1497.e4
JournalCurrent Biology
Volume27
Issue number10
DOIs
StatePublished - May 22 2017
Externally publishedYes

Bibliographical note

Funding Information:
We are grateful to Jenny Benanti, Dan McCollum, Peter Pryciak, and members of the Benanti and Rhind laboratories for insightful suggestions on this work and constructive comments on the manuscript. We acknowledge the pioneering work in the Mitchison laboratory on the phenomenon of excess mitotic delay, and thank Alan Herring for discussing his unpublished work on the subject. We thank Snezhana Oliferenko for the GST-NLS-mCherry construct, and Bela Novak for help recreating his fission yeast cell-cycle model. This work was supported by the NIH GM098815 (to N.R.) and the Medical Research Council (to S.M.). This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344 (LLNL-ABS-691918).

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • Cdc25
  • S. pombe
  • cell size
  • excess mitotic delay
  • unstable activator

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