Noisy Cell-Size-Correlated Expression of Cyclin B Drives Probabilistic Cell-Size Homeostasis in Fission Yeast

James O. Patterson, Paul Rees, Paul Nurse

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

How cells correct deviations from a mean cell size at mitosis remains uncertain. Classical cell-size homeostasis models are the sizer, timer, and adder [1]. Sizers postulate that cells divide at some threshold size; timers, that cells grow for a set time; and adders, that cells add a constant volume before division. Here, we show that a size-based probabilistic model of cell-size control at the G2/M transition (P(Div)) can generate realistic cell-size homeostasis in silico. In fission yeast cells, Cyclin B Cdc13 scales with size, and we propose that this increases the likelihood of mitotic entry, while molecular noise in its expression adds a probabilistic component to the model. Varying Cdc13 expression levels exogenously using a newly developed tetracycline inducible promoter shows that both the level and variability of its expression influence cell size at division. Our results demonstrate that as cells grow larger, their probability of dividing increases, and this is sufficient to generate cell-size homeostasis. Size-correlated Cdc13 expression forms part of the molecular circuitry of this system.

Original languageEnglish (US)
Pages (from-to)1379-1386.e4
JournalCurrent Biology
Volume29
Issue number8
DOIs
StatePublished - Apr 22 2019

Keywords

  • CDK
  • cell division
  • cell growth
  • cell size
  • cyclin
  • cyclin-dependent kinase
  • mitosis
  • single-cell biology
  • systems biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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