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dc.contributor.authorJohnson, Mark C
dc.contributor.authorCan, Geylani
dc.contributor.authorSantos, Miguel Monteiro
dc.contributor.authorAlexander, Diana
dc.contributor.authorZegerman, Philip
dc.date.accessioned2021-01-14T05:16:55Z
dc.date.available2021-01-14T05:16:55Z
dc.date.issued2021-01-05
dc.date.submitted2020-09-29
dc.identifier.other63589
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316169
dc.description.abstractCheckpoints maintain the order of cell cycle events during DNA damage or incomplete replication. How the checkpoint response is tailored to different phases of the cell cycle remains poorly understood. The S-phase checkpoint for example results in the slowing of replication, which in budding yeast occurs by Rad53-dependent inhibition of the initiation factors Sld3 and Dbf4. Despite this, we show here that Rad53 phosphorylates both of these substrates throughout the cell cycle at the same sites as in S-phase, suggesting roles for this pathway beyond S-phase. Indeed, we show that Rad53-dependent inhibition of Sld3 and Dbf4 limits re-replication in G2/M, preventing gene amplification. In addition, we show that inhibition of Sld3 and Dbf4 in G1 prevents premature initiation at all origins at the G1/S transition. This study redefines the scope of the ‘S-phase checkpoint’ with implications for understanding checkpoint function in cancers that lack cell cycle controls.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectChromosomes and Gene Expression
dc.subjectcell cycle
dc.subjectcheckpoints
dc.subjectS-phase
dc.subjectreplication
dc.subjectRad53
dc.subjectgenome stability
dc.subjectS. cerevisiae
dc.titleCheckpoint inhibition of origin firing prevents inappropriate replication outside of S-phase
dc.typeArticle
dc.date.updated2021-01-14T05:16:55Z
prism.publicationNameeLife
prism.volume10
dc.identifier.doi10.17863/CAM.63277
dcterms.dateAccepted2021-01-04
rioxxterms.versionofrecord10.7554/elife.63589
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Formosa, Tim
datacite.contributor.supervisorsenior_editor: Struhl, Kevin
dc.contributor.orcidJohnson, Mark C [0000-0002-6136-7055]
dc.contributor.orcidCan, Geylani [0000-0002-1716-7830]
dc.contributor.orcidSantos, Miguel Monteiro [0000-0002-5594-2682]
dc.contributor.orcidAlexander, Diana [0000-0002-7785-3170]
dc.contributor.orcidZegerman, Philip [0000-0002-5707-1083]
dc.identifier.eissn2050-084X
pubs.funder-project-idWorldwide Cancer Research (AICR 10-0908)
pubs.funder-project-idWellcome Trust (107056/Z/15/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M011194/1)
pubs.funder-project-idCancer Research UK (C15873/A12700)
pubs.funder-project-idCancer Research UK (C6946/A14492)
pubs.funder-project-idWellcome Trust (092096)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)