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Clb3-centered regulations are recurrent across distinctparameter regions in minimal autonomous cell cycle oscillatordesigns

Mondeel, Thierry D.G.A, Ivanov, Oleksandr, Westerhoff, Hans V., Liebermeister, Wolfram and Barberis, Matteo (2020) Clb3-centered regulations are recurrent across distinctparameter regions in minimal autonomous cell cycle oscillatordesigns NPJ Systems Biology and Applications, 6 (1), 8.

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Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryoticcell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specifictiming and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced celldivision. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that aminimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) andClb3-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 evolutionaryconservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional (“healthy”) phenotypes require thecapacity to oscillate autonomously whereas dysfunctional (potentially“diseased”) phenotypes may lack this capacity.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Mondeel, Thierry D.G.A
Ivanov, Oleksandr
Westerhoff, Hans V.
Liebermeister, Wolfram
Date : 3 April 2020
Funders : University of Surrey - Systems Biology Grant, University of Amsterdam - SILS Starting Grant
DOI : 10.1038/s41540-020-0125-0
Copyright Disclaimer : © The Author(s) 2020 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Depositing User : James Marshall
Date Deposited : 18 Jun 2020 08:55
Last Modified : 18 Jun 2020 08:55

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