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A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability

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dc.contributor.authorBarik, Debashisen
dc.contributor.authorBall, David A.en
dc.contributor.authorPeccoud, Jeanen
dc.contributor.authorTyson, John J.en
dc.date.accessioned2018-11-19T18:38:15Zen
dc.date.available2018-11-19T18:38:15Zen
dc.date.issued2016-12en
dc.description.abstractThe cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of similar to 30 mutant yeast strains that have not yet been characterized experimentally.en
dc.description.sponsorshipThis work was supported by funding from the University Grants Commission (India) Start-Up Research Grant F30-24/2014(BSR) to DB and from the National Institutes of Health (USA) 1R01-GM078989-09 to JJT and JP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1005230en
dc.identifier.eissn1553-7358en
dc.identifier.issn1553-734Xen
dc.identifier.issue12en
dc.identifier.othere1005230en
dc.identifier.pmid27935947en
dc.identifier.urihttp://hdl.handle.net/10919/85908en
dc.identifier.volume12en
dc.language.isoen_USen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmultisite protein-phosphorylationen
dc.subjectapc-dependent proteolysisen
dc.subjectbudding-yeasten
dc.subjectsaccharomyces-cerevisiaeen
dc.subjectgene-expressionen
dc.subjectmitotic exiten
dc.subjectpositive feedbacken
dc.subjectg1 cyclinsen
dc.subjectphosphatase cdc14en
dc.subjectdna-replicationen
dc.titleA Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variabilityen
dc.title.serialPLOS Computational Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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