A model of yeast cell-cycle regulation based on multisite phosphorylation

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dc.contributor.authorBarik, Debashisen
dc.contributor.authorBaumann, William T.en
dc.contributor.authorPaul, Mark R.en
dc.contributor.authorNovak, Belaen
dc.contributor.authorTyson, John J.en
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2016-12-09T21:35:55Zen
dc.date.available2016-12-09T21:35:55Zen
dc.date.issued2010-08-01en
dc.description.abstractIn order for the cell’s genome to be passed intact from one generation to the next, the events of the cell cycle (DNA replication, mitosis, cell division) must be executed in the correct order, despite the considerable molecular noise inherent in any protein-based regulatory system residing in the small confines of a eukaryotic cell. To assess the effects of molecular fluctuations on cell-cycle progression in budding yeast cells, we have constructed a new model of the regulation of Cln- and Clb-dependent kinases, based on multisite phosphorylation of their target proteins and on positive and negative feedback loops involving the kinases themselves. To account for the significant role of noise in the transcription and translation steps of gene expression, the model includes mRNAs as well as proteins. The model equations are simulated deterministically and stochastically to reveal the bistable switching behavior on which proper cell-cycle progression depends and to show that this behavior is robust to the level of molecular noise expected in yeast-sized cells (B50 fL volume). The model gives a quantitatively accurate account of the variability observed in the G1-S transition in budding yeast, which is governed by an underlying sizer + timer control system.en
dc.description.versionPublished versionen
dc.format.extent18 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/msb.2010.55en
dc.identifier.issn1744-4292en
dc.identifier.urihttp://hdl.handle.net/10919/73634en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000284527700002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectbistabilityen
dc.subjectcell-cycle variabilityen
dc.subjectsize controlen
dc.subjectstochastic modelen
dc.subjecttranscription-translation couplingen
dc.subjectANAPHASE-PROMOTING COMPLEXen
dc.subjectSACCHAROMYCES-CEREVISIAEen
dc.subjectBUDDING YEASTen
dc.subjectG1 CYCLINSen
dc.subjectPHOSPHATASE CDC14en
dc.subjectGENE-EXPRESSIONen
dc.subjectS-PHASEen
dc.subjectG1-SPECIFIC TRANSCRIPTIONen
dc.subjectPROTEIN-PHOSPHORYLATIONen
dc.subjectPOSITIVE FEEDBACKen
dc.titleA model of yeast cell-cycle regulation based on multisite phosphorylationen
dc.title.serialMolecular Systems Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineering/Electrical and Computer Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Mechanical Engineeringen
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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