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Positive feedback of G1 cyclins ensures coherent cell cycle entry

Author

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  • Jan M. Skotheim

    (Center for Studies in Physics and Biology, The Rockefeller University,)

  • Stefano Di Talia

    (Center for Studies in Physics and Biology, The Rockefeller University,)

  • Eric D. Siggia

    (Center for Studies in Physics and Biology, The Rockefeller University,)

  • Frederick R. Cross

    (The Rockefeller University, 1230 York Avenue, New York 10065, USA)

Abstract

In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates multiple internal and external signals into an all-or-none decision to enter the cell cycle. Here we show that Start behaves like a switch due to systems-level feedback in the regulatory network. In contrast to current models proposing a linear cascade of Start activation, transcriptional positive feedback of the G1 cyclins Cln1 and Cln2 induces the near-simultaneous expression of the ∼200-gene G1/S regulon. Nuclear Cln2 drives coherent regulon expression, whereas cytoplasmic Cln2 drives efficient budding. Cells with the CLN1 and CLN2 genes deleted frequently arrest as unbudded cells, incurring a large fluctuation-induced fitness penalty due to both the lack of cytoplasmic Cln2 and insufficient G1/S regulon expression. Thus, positive-feedback-amplified expression of Cln1 and Cln2 simultaneously drives robust budding and rapid, coherent regulon expression. A similar G1/S regulatory network in mammalian cells, comprised of non-orthologous genes, suggests either conservation of regulatory architecture or convergent evolution.

Suggested Citation

  • Jan M. Skotheim & Stefano Di Talia & Eric D. Siggia & Frederick R. Cross, 2008. "Positive feedback of G1 cyclins ensures coherent cell cycle entry," Nature, Nature, vol. 454(7202), pages 291-296, July.
    • Handle: RePEc:nat:nature:v:454:y:2008:i:7202:d:10.1038_nature07118
    DOI: 10.1038/nature07118
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    Cited by:

    1. Vojislav Gligorovski & Ahmad Sadeghi & Sahand Jamal Rahi, 2023. "Multidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Andreas Doncic & Umut Eser & Oguzhan Atay & Jan M Skotheim, 2013. "An Algorithm to Automate Yeast Segmentation and Tracking," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-11, March.
    3. Anneke Brümmer & Carlos Salazar & Vittoria Zinzalla & Lilia Alberghina & Thomas Höfer, 2010. "Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication," PLOS Computational Biology, Public Library of Science, vol. 6(5), pages 1-13, May.

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