Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs

Thierry D.G.A. Mondeel, Oleksandr Ivanov, Hans V. Westerhoff, Wolfram Liebermeister, Matteo Barberis

Research output: Contribution to JournalArticleAcademicpeer-review


Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that a minimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) and Clb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionary conservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional ("healthy") phenotypes require the capacity to oscillate autonomously whereas dysfunctional (potentially "diseased") phenotypes may lack this capacity.

Original languageEnglish
Article number8
Pages (from-to)1-15
Number of pages15
JournalNPJ systems biology and applications
Issue number1
Publication statusPublished - 3 Apr 2020


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