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dc.contributor.authorBigot, Nen_US
dc.contributor.authorDay, Men_US
dc.contributor.authorBaldock, RAen_US
dc.contributor.authorWatts, FZen_US
dc.contributor.authorOliver, AWen_US
dc.contributor.authorPearl, LHen_US
dc.date.accessioned2020-03-06T12:40:52Z
dc.date.issued2019-05-28en_US
dc.identifier.citationeLife, 2019, 8en_US
dc.identifier.issn2050-084Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3538
dc.identifier.eissn2050-084Xen_US
dc.identifier.doi10.7554/elife.44353en_US
dc.description.abstractCoordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1. Mutation of these sites does not affect formation of 53BP1 or ATM foci following DNA damage, but abolishes recruitment of TOPBP1, ATR and CHK1 to 53BP1 damage foci, abrogating cell cycle arrest and permitting progression into S-phase. TOPBP1 interaction with 53BP1 is structurally complimentary to its interaction with RAD9-RAD1-HUS1, allowing these damage recognition factors to bind simultaneously to the same TOPBP1 molecule and cooperate in ATR activation in the G1 DNA damage checkpoint.en_US
dc.formatElectronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHela Cellsen_US
dc.subjectHumansen_US
dc.subjectDNA Damageen_US
dc.subjectMultiprotein Complexesen_US
dc.subjectCarrier Proteinsen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectNuclear Proteinsen_US
dc.subjectS Phaseen_US
dc.subjectDNA Replicationen_US
dc.subjectProtein Processing, Post-Translationalen_US
dc.subjectProtein Conformationen_US
dc.subjectProtein Bindingen_US
dc.subjectMethylationen_US
dc.subjectPhosphorylationen_US
dc.subjectUbiquitinationen_US
dc.subjectCell Cycle Checkpointsen_US
dc.subjectAtaxia Telangiectasia Mutated Proteinsen_US
dc.subjectCheckpoint Kinase 1en_US
dc.subjectTumor Suppressor p53-Binding Protein 1en_US
dc.subjectProtein Domainsen_US
dc.titlePhosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-25en_US
rioxxterms.versionofrecord10.7554/elife.44353en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-05-28en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfeLifeen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.publication-statusPublisheden_US
pubs.volume8en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorPearl, Laurenceen_US


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