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dc.contributor.authorLi, X
dc.contributor.authorBaek, G
dc.contributor.authorRamanand, SG
dc.contributor.authorSharp, A
dc.contributor.authorGao, Y
dc.contributor.authorYuan, W
dc.contributor.authorWelti, J
dc.contributor.authorRodrigues, DN
dc.contributor.authorDolling, D
dc.contributor.authorFigueiredo, I
dc.contributor.authorSumanasuriya, S
dc.contributor.authorCrespo, M
dc.contributor.authorAslam, A
dc.contributor.authorLi, R
dc.contributor.authorYin, Y
dc.contributor.authorMukherjee, B
dc.contributor.authorKanchwala, M
dc.contributor.authorHughes, AM
dc.contributor.authorHalsey, WS
dc.contributor.authorChiang, C-M
dc.contributor.authorXing, C
dc.contributor.authorRaj, GV
dc.contributor.authorBurma, S
dc.contributor.authorde Bono, J
dc.contributor.authorMani, RS
dc.date.accessioned2019-07-17T09:06:23Z
dc.date.issued2018-01
dc.identifier.citationCell reports, 2018, 22 (3), pp. 796 - 808
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3291
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2017.12.078
dc.description.abstractBRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin reader proteins that bind acetylated histones and regulate gene expression. Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated antitumor activity against multiple cancer types. We show that BRD4 is essential for the repair of DNA double-strand breaks (DSBs) and mediates the formation of oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ) pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced acetylation of histone H4, leading to BRD4 recruitment, and stable establishment of the DNA repair complex. In support of this, we also show that, in clinical tumor samples, BRD4 protein levels are negatively associated with outcome after prostate cancer (PCa) radiation therapy. Thus, in addition to regulating gene expression, BRD4 is also a central player in the repair of DNA DSBs, with significant implications for cancer therapy.
dc.formatPrint
dc.format.extent796 - 808
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectChromatin
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectDNA Damage
dc.subjectCell Cycle Proteins
dc.subjectOncogene Proteins, Fusion
dc.subjectNuclear Proteins
dc.subjectHistones
dc.subjectTranscription Factors
dc.subjectGene Fusion
dc.subjectGene Rearrangement
dc.subjectAcetylation
dc.subjectMale
dc.subjectDNA End-Joining Repair
dc.titleBRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene Rearrangements in Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-12-21
rioxxterms.versionofrecord10.1016/j.celrep.2017.12.078
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue3
pubs.notesNot 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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume22
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamTranslational Therapeuticsen_US
dc.contributor.icrauthorSumanasuriya, Seminien
dc.contributor.icrauthorSharp, Adamen
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorCrespo, Mateusen


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