dc.contributor.author | Li, X | |
dc.contributor.author | Baek, G | |
dc.contributor.author | Ramanand, SG | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | Gao, Y | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Welti, J | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Sumanasuriya, S | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Aslam, A | |
dc.contributor.author | Li, R | |
dc.contributor.author | Yin, Y | |
dc.contributor.author | Mukherjee, B | |
dc.contributor.author | Kanchwala, M | |
dc.contributor.author | Hughes, AM | |
dc.contributor.author | Halsey, WS | |
dc.contributor.author | Chiang, C-M | |
dc.contributor.author | Xing, C | |
dc.contributor.author | Raj, GV | |
dc.contributor.author | Burma, S | |
dc.contributor.author | de Bono, J | |
dc.contributor.author | Mani, RS | |
dc.date.accessioned | 2019-07-17T09:06:23Z | |
dc.date.issued | 2018-01-16 | |
dc.identifier.citation | Cell reports, 2018, 22 (3), pp. 796 - 808 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3291 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2017.12.078 | |
dc.description.abstract | BRD4 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.format | Print | |
dc.format.extent | 796 - 808 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Chromatin | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Oncogene Proteins, Fusion | |
dc.subject | Nuclear Proteins | |
dc.subject | Histones | |
dc.subject | Transcription Factors | |
dc.subject | Gene Fusion | |
dc.subject | Gene Rearrangement | |
dc.subject | Acetylation | |
dc.subject | Male | |
dc.subject | DNA End-Joining Repair | |
dc.title | BRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene Rearrangements in Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-21 | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2017.12.078 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2018-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell reports | |
pubs.issue | 3 | |
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 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-status | Published | |
pubs.volume | 22 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Translational Therapeutics | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | Sumanasuriya, Semini | |
dc.contributor.icrauthor | De Bono, Johann | |