dc.contributor.author | Hodson, C | |
dc.contributor.author | van Twest, S | |
dc.contributor.author | Dylewska, M | |
dc.contributor.author | O'Rourke, JJ | |
dc.contributor.author | Tan, W | |
dc.contributor.author | Murphy, VJ | |
dc.contributor.author | Walia, M | |
dc.contributor.author | Abbouche, L | |
dc.contributor.author | Nieminuszczy, J | |
dc.contributor.author | Dunn, E | |
dc.contributor.author | Bythell-Douglas, R | |
dc.contributor.author | Heierhorst, J | |
dc.contributor.author | Niedzwiedz, W | |
dc.contributor.author | Deans, AJ | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-03-03T12:50:43Z | |
dc.date.available | 2023-03-03T12:50:43Z | |
dc.date.issued | 2022-12-06 | |
dc.identifier | ARTN 111749 | |
dc.identifier | S2211-1247(22)01632-1 | |
dc.identifier.citation | Cell Reports, 2022, 41 (10), pp. 111749 - | en_US |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5702 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.eissn | 2211-1247 | |
dc.identifier.doi | 10.1016/j.celrep.2022.111749 | |
dc.description.abstract | Co-transcriptional R loops arise from stalling of RNA polymerase, leading to the formation of stable DNA:RNA hybrids. Unresolved R loops promote genome instability but are counteracted by helicases and nucleases. Here, we show that branchpoint translocases are a third class of R-loop-displacing enzyme in vitro. In cells, deficiency in the Fanconi-anemia-associated branchpoint translocase FANCM causes R-loop accumulation, particularly after treatment with DNA:RNA-hybrid-stabilizing agents. This correlates with FANCM localization at R-loop-prone regions of the genome. Moreover, other branchpoint translocases associated with human disease, such as SMARCAL1 and ZRANB3, and those from lower organisms can also remove R loops in vitro. Branchpoint translocases are more potent than helicases in resolving R loops, indicating their evolutionary important role in R-loop suppression. In human cells, FANCM, SMARCAL1, and ZRANB3 depletion causes additive effects on R-loop accumulation and DNA damage. Our work reveals a mechanistic basis for R-loop displacement that is linked to genome stability. | |
dc.format | Print | |
dc.format.extent | 111749 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | CELL PRESS | en_US |
dc.relation.ispartof | Cell Reports | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | CP: Molecular biology | |
dc.subject | DNA:RNA hybrid | |
dc.subject | Fanconi anemia | |
dc.subject | R loop | |
dc.subject | genome stability | |
dc.subject | human disease | |
dc.subject | transcription | |
dc.subject | translocation | |
dc.subject | Humans | |
dc.subject | R-Loop Structures | |
dc.subject | RNA | |
dc.subject | DNA Helicases | |
dc.title | Branchpoint translocation by fork remodelers as a general mechanism of R-loop removal. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-11-09 | |
dc.date.updated | 2023-03-03T12:50:00Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1016/j.celrep.2022.111749 | en_US |
rioxxterms.licenseref.startdate | 2022-12-06 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36476850 | |
pubs.issue | 10 | |
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/Cancer and Genome Instability | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.celrep.2022.111749 | |
pubs.volume | 41 | |
icr.researchteam | Cancer and Genome Instab | en_US |
dc.contributor.icrauthor | Niedzwiedz, Wojciech | |
icr.provenance | Deposited by Mr Arek Surman on 2023-03-03. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S2211124722016321-main.pdf | |