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Experimental testing of a new integrated model of the budding yeast Start transition

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dc.contributor.authorAdames, Neil R.en
dc.contributor.authorSchuck, P. Loganen
dc.contributor.authorChen, Katherine C.en
dc.contributor.authorMurali, T. M.en
dc.contributor.authorTyson, John J.en
dc.contributor.authorPeccoud, Jeanen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentComputer Scienceen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentInstitute for Critical Technology and Applied Scienceen
dc.date.accessioned2016-12-09T21:29:48Zen
dc.date.available2016-12-09T21:29:48Zen
dc.date.issued2015-11-05en
dc.description.abstractThe cell cycle is composed of bistable molecular switches that govern the transitions between gap phases (G1 and G2) and the phases in which DNA is replicated (S) and partitioned between daughter cells (M). Many molecular details of the budding yeast G1–S transition (Start) have been elucidated in recent years, especially with regard to its switch-like behavior due to positive feedback mechanisms. These results led us to reevaluate and expand a previous mathematical model of the yeast cell cycle. The new model incorporates Whi3 inhibition of Cln3 activity, Whi5 inhibition of SBF and MBF transcription factors, and feedback inhibition of Whi5 by G1–S cyclins. We tested the accuracy of the model by simulating various mutants not described in the literature. We then constructed these novel mutant strains and compared their observed phenotypes to the model’s simulations. The experimental results reported here led to further changes of the model, which will be fully described in a later article. Our study demonstrates the advantages of combining model design, simulation, and testing in a coordinated effort to better understand a complex biological network.en
dc.description.versionPublished versionen
dc.format.extent3966 - 3984 (19) page(s)en
dc.identifier.doihttps://doi.org/10.1091/mbc.E15-06-0358en
dc.identifier.issn1059-1524en
dc.identifier.issue22en
dc.identifier.urihttp://hdl.handle.net/10919/73622en
dc.identifier.volume26en
dc.languageEnglishen
dc.publisherAmerican Society for Cell Biologyen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000366324900013&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.subjectCell Biologyen
dc.subjectCELL-CYCLE STARTen
dc.subjectSYSTEMS-LEVEL FEEDBACKen
dc.subjectCDC28 PROTEIN-KINASEen
dc.subjectSACCHAROMYCES-CEREVISIAEen
dc.subjectTRANSCRIPTION FACTORen
dc.subjectSIZE-CONTROLen
dc.subjectG1 CYCLINSen
dc.subjectDNA-REPLICATIONen
dc.subjectS-PHASEen
dc.subjectCLN3-CDC28 KINASEen
dc.titleExperimental testing of a new integrated model of the budding yeast Start transitionen
dc.title.serialMolecular Biology of The Cellen
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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