Analysis of a generic model of eukaryotic cell-cycle regulation

dc.contributorVirginia Techen
dc.contributor.authorCsikasz-Nagy, A.en
dc.contributor.authorBattogtokh, D.en
dc.contributor.authorChen, Katherine C.en
dc.contributor.authorNovak, Belaen
dc.contributor.authorTyson, John J.en
dc.contributor.departmentBiological Sciencesen
dc.date.accessed2014-02-05en
dc.date.accessioned2014-02-26T19:10:06Zen
dc.date.available2014-02-26T19:10:06Zen
dc.date.issued2006-06en
dc.description.abstractWe propose a protein interaction network for the regulation of DNA synthesis and mitosis that emphasizes the universality of the regulatory system among eukaryotic cells. The idiosyncrasies of cell cycle regulation in particular organisms can be attributed, we claim, to specific settings of rate constants in the dynamic network of chemical reactions. The values of these rate constants are determined ultimately by the genetic makeup of an organism. To support these claims, we convert the reaction mechanism into a set of governing kinetic equations and provide parameter values (specific to budding yeast, fission yeast, frog eggs, and mammalian cells) that account for many curious features of cell cycle regulation in these organisms. Using one-parameter bifurcation diagrams, we show how overall cell growth drives progression through the cell cycle, how cell-size homeostasis can be achieved by two different strategies, and how mutations remodel bifurcation diagrams and create unusual cell-division phenotypes. The relation between gene dosage and phenotype can be summarized compactly in two-parameter bifurcation diagrams. Our approach provides a theoretical framework in which to understand both the universality and particularity of cell cycle regulation, and to construct, in modular fashion, increasingly complex models of the networks controlling cell growth and division.en
dc.description.sponsorshipDefense Advanced Research Project Agency AFRL F30602-02-0572en
dc.description.sponsorshipJames S. McDonnell Foundation 21002050en
dc.description.sponsorshipEuropean Commission COMBIO, LSHG-CT-503568en
dc.identifier.citationCsikasz-Nagy, A; Battogtokh, D; Chen, KC; et al. "Analysis of a generic model of eukaryotic cell-cycle regulation," Biophysical Journal 90(12), 4361-4379 (2006); doi: 10.1529/biophysj.106.081240en
dc.identifier.doihttps://doi.org/10.1529/biophysj.106.081240en
dc.identifier.issn0006-3495en
dc.identifier.urihttp://hdl.handle.net/10919/25782en
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0006349506726145en
dc.language.isoen_USen
dc.publisherCELL PRESSen
dc.rightsIn Copyrighten
dc.rights.holderBiophysical Societyen
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectprotein-protein interactionsen
dc.subjectanaphase-promoting complexen
dc.subjectapc-dependenten
dc.subjectproteolysisen
dc.subjectxenopus-oocyte extractsen
dc.subjectm-phase controlen
dc.subjectfission yeasten
dc.subjectsaccharomyces-cerevisiaeen
dc.subjectmathematical-modelen
dc.subjectbifurcation-analysisen
dc.subjectdna-replicationen
dc.titleAnalysis of a generic model of eukaryotic cell-cycle regulationen
dc.title.serialBiophysical Journalen
dc.typeArticle - Refereeden

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