Cell Cycle Control by a Minimal Cdk Network

dc.contributor.authorGerard, Claudeen
dc.contributor.authorTyson, John J.en
dc.contributor.authorCoudreuse, Damienen
dc.contributor.authorNovak, Belaen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2016-12-09T21:33:39Zen
dc.date.available2016-12-09T21:33:39Zen
dc.date.issued2015-02-01en
dc.description.abstractIn present-day eukaryotes, the cell division cycle is controlled by a complex network of interacting proteins, including members of the cyclin and cyclin-dependent protein kinase (Cdk) families, and the Anaphase Promoting Complex (APC). Successful progression through the cell cycle depends on precise, temporally ordered regulation of the functions of these proteins. In light of this complexity, it is surprising that in fission yeast, a minimal Cdk network consisting of a single cyclin-Cdk fusion protein can control DNA synthesis and mitosis in a manner that is indistinguishable from wild type. To improve our understanding of the cell cycle regulatory network, we built and analysed a mathematical model of the molecular interactions controlling the G1/S and G2/M transitions in these minimal cells. The model accounts for all observed properties of yeast strains operating with the fusion protein. Importantly, coupling the model’s predictions with experimental analysis of alternative minimal cells, we uncover an explanation for the unexpected fact that elimination of inhibitory phosphorylation of Cdk is benign in these strains while it strongly affects normal cells. Furthermore, in the strain without inhibitory phosphorylation of the fusion protein, the distribution of cell size at division is unusually broad, an observation that is accounted for by stochastic simulations of the model. Our approach provides novel insights into the organization and quantitative regulation of wild type cell cycle progression. In particular, it leads us to propose a new mechanistic model for the phenomenon of mitotic catastrophe, relying on a combination of unregulated, multi-cyclin-dependent Cdk activities.en
dc.description.versionPublished versionen
dc.format.extent? - ? (27) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1004056en
dc.identifier.issn1553-734Xen
dc.identifier.issue2en
dc.identifier.urihttp://hdl.handle.net/10919/73629en
dc.identifier.volume11en
dc.languageEnglishen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352081000022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemical Research Methodsen
dc.subjectMathematical & Computational Biologyen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectFISSION YEASTen
dc.subjectS-PHASEen
dc.subjectDNA-REPLICATIONen
dc.subjectPROTEIN-KINASEen
dc.subjectSCHIZOSACCHAROMYCES-POMBEen
dc.subjectMULTISITE PHOSPHORYLATIONen
dc.subjectTYROSINE PHOSPHORYLATIONen
dc.subjectGENE-EXPRESSIONen
dc.subjectMITOTIC CONTROLen
dc.subjectFEEDBACK LOOPSen
dc.titleCell Cycle Control by a Minimal Cdk Networken
dc.title.serialPLOS Computational Biologyen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Distinguished Professorsen
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