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dc.contributor.authorMeisenberg, Cen_US
dc.contributor.authorPinder, SIen_US
dc.contributor.authorHopkins, SRen_US
dc.contributor.authorWooller, SKen_US
dc.contributor.authorBenstead-Hume, Gen_US
dc.contributor.authorPearl, FMGen_US
dc.contributor.authorJeggo, PAen_US
dc.contributor.authorDowns, JAen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-12T09:52:37Z
dc.date.issued2019-01-17en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30554942en_US
dc.identifierS1097-2765(18)30943-2en_US
dc.identifier.citationMol Cell, 2019, 73 (2), pp. 212 - 223.e7en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3047
dc.identifier.eissn1097-4164en_US
dc.identifier.doi10.1016/j.molcel.2018.11.001en_US
dc.description.abstractCohesin subunits are frequently mutated in cancer, but how they function as tumor suppressors is unknown. Cohesin mediates sister chromatid cohesion, but this is not always perturbed in cancer cells. Here, we identify a previously unknown role for cohesin. We find that cohesin is required to repress transcription at DNA double-strand breaks (DSBs). Notably, cohesin represses transcription at DSBs throughout interphase, indicating that this is distinct from its known role in mediating DNA repair through sister chromatid cohesion. We identified a cancer-associated SA2 mutation that supports sister chromatid cohesion but is unable to repress transcription at DSBs. We further show that failure to repress transcription at DSBs leads to large-scale genome rearrangements. Cancer samples lacking SA2 display mutational patterns consistent with loss of this pathway. These findings uncover a new function for cohesin that provides insights into its frequent loss in cancer.en_US
dc.format.extent212 - 223.e7en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDNA repairen_US
dc.subjectPBAFen_US
dc.subjectPBRM1en_US
dc.subjectSA2en_US
dc.subjectSMARCA4en_US
dc.subjectSTAG2en_US
dc.subjectSWI/SNFen_US
dc.subjectcanceren_US
dc.subjecttranscriptional silencingen_US
dc.titleRepression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-11-01en_US
rioxxterms.versionofrecord10.1016/j.molcel.2018.11.001en_US
rioxxterms.licenseref.startdate2019-01-17en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMol Cellen_US
pubs.issue2en_US
pubs.notesNot knownen_US
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/Epigenetics and Genome Stability
pubs.publication-statusPublisheden_US
pubs.volume73en_US
pubs.embargo.termsNot knownen_US
icr.researchteamEpigenetics and Genome Stabilityen_US
dc.contributor.icrauthorDowns, Jessicaen_US


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