dc.contributor.author | Barr, AR | |
dc.contributor.author | Heldt, FS | |
dc.contributor.author | Zhang, T | |
dc.contributor.author | Bakal, C | |
dc.contributor.author | Novák, B | |
dc.date.accessioned | 2020-06-26T09:53:09Z | |
dc.date.issued | 2016-01-27 | |
dc.identifier.citation | Cell systems, 2016, 2 (1), pp. 27 - 37 | |
dc.identifier.issn | 2405-4712 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3778 | |
dc.identifier.eissn | 2405-4720 | |
dc.identifier.doi | 10.1016/j.cels.2016.01.001 | |
dc.description.abstract | The transition from G1 into DNA replication (S phase) is an emergent behavior resulting from dynamic and complex interactions between cyclin-dependent kinases (Cdks), Cdk inhibitors (CKIs), and the anaphase-promoting complex/cyclosome (APC/C). Understanding the cellular decision to commit to S phase requires a quantitative description of these interactions. We apply quantitative imaging of single human cells to track the expression of G1/S regulators and use these data to parametrize a stochastic mathematical model of the G1/S transition. We show that a rapid, proteolytic, double-negative feedback loop between Cdk2:Cyclin and the Cdk inhibitor p27(Kip1) drives a switch-like entry into S phase. Furthermore, our model predicts that increasing Emi1 levels throughout S phase are critical in maintaining irreversibility of the G1/S transition, which we validate using Emi1 knockdown and live imaging of G1/S reporters. This work provides insight into the general design principles of the signaling networks governing the temporally abrupt transitions between cell-cycle phases. | |
dc.format | Print-Electronic | |
dc.format.extent | 27 - 37 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Cell Cycle Proteins | |
dc.subject | G1 Phase | |
dc.subject | S Phase | |
dc.subject | Cell Cycle Checkpoints | |
dc.subject | Anaphase-Promoting Complex-Cyclosome | |
dc.title | A Dynamical Framework for the All-or-None G1/S Transition. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-01-04 | |
rioxxterms.versionofrecord | 10.1016/j.cels.2016.01.001 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-01-27 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell systems | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems | |
pubs.publication-status | Published | |
pubs.volume | 2 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Dynamical Cell Systems | |
dc.contributor.icrauthor | Barr, Alexis | |
dc.contributor.icrauthor | Bakal, Christopher | |