Irreversibility of mitotic exit is the consequence of systems-level feedback

Sandra López-Avilés, Orsolya Kapuy, Béla Novák and Frank Uhlmann ()
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Sandra López-Avilés: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
Orsolya Kapuy: Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Béla Novák: Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Frank Uhlmann: Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK

Nature, 2009, vol. 459, issue 7246, 592-595

Abstract: Mitotic exit: no turning back The eukaryotic cell cycle comprises an ordered series of events orchestrated by cyclin-dependent kinases (Cdks), with unidirectional cell-cycle transitions being required for its successful completion. Proteolytic degradation of cyclins has been assumed to be responsible for the irreversible transitions. Here, the contribution of cyclin proteolysis to the irreversibility of mitotic exit has been examined with a combination of experiments in budding yeast and mathematical modelling. Although forced cyclin degradation can drive mitotic exit, it is not sufficient for irreversibility, due to the re-synthesis of cyclin. Mitotic exit becomes irreversible only after longer periods of cyclin degradation and activation of a double negative feedback loop involving the Cdk inhibitor Sic1.

Date: 2009
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DOI: 10.1038/nature07984

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