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

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 occu...

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Autores principales: Mondeel, Thierry D. G. A., Ivanov, Oleksandr, Westerhoff, Hans V., Liebermeister, Wolfram, Barberis, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125140/
https://www.ncbi.nlm.nih.gov/pubmed/32245958
http://dx.doi.org/10.1038/s41540-020-0125-0
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author Mondeel, Thierry D. G. A.
Ivanov, Oleksandr
Westerhoff, Hans V.
Liebermeister, Wolfram
Barberis, Matteo
author_facet Mondeel, Thierry D. G. A.
Ivanov, Oleksandr
Westerhoff, Hans V.
Liebermeister, Wolfram
Barberis, Matteo
author_sort Mondeel, Thierry D. G. A.
collection PubMed
description 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.
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spelling pubmed-71251402020-04-13 Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs Mondeel, Thierry D. G. A. Ivanov, Oleksandr Westerhoff, Hans V. Liebermeister, Wolfram Barberis, Matteo NPJ Syst Biol Appl Article 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. Nature Publishing Group UK 2020-04-03 /pmc/articles/PMC7125140/ /pubmed/32245958 http://dx.doi.org/10.1038/s41540-020-0125-0 Text en © 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 give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated 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 http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mondeel, Thierry D. G. A.
Ivanov, Oleksandr
Westerhoff, Hans V.
Liebermeister, Wolfram
Barberis, Matteo
Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title_full Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title_fullStr Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title_full_unstemmed Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title_short Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
title_sort clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125140/
https://www.ncbi.nlm.nih.gov/pubmed/32245958
http://dx.doi.org/10.1038/s41540-020-0125-0
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