{"doi":"10.1016/j.molcel.2015.01.011","title":"BRCA1 Recruitment to Transcriptional Pause Sites Is Required for R-Loop-Driven DNA Damage Repair","abstract":"The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions. There it mediates the recruitment of a specific, physiological binding partner, senataxin (SETX). Disruption of this complex led to R-loop-driven DNA damage at those loci as reflected by adjacent γ-H2AX accumulation and ssDNA breaks within the untranscribed strand of relevant R-loop structures. Genome-wide analysis revealed widespread BRCA1 binding enrichment at R-loop-rich termination regions (TRs) of actively transcribed genes. Strikingly, within some of these genes in BRCA1 null breast tumors, there are specific insertion/deletion mutations located close to R-loop-mediated BRCA1 binding sites within TRs. Thus, BRCA1/SETX complexes support a DNA repair mechanism that addresses R-loop-based DNA damage at transcriptional pause sites.","journal":"Molecular Cell","year":2015,"id":2506,"datarank":0.9241810982542616,"base_score":6.161207321695077,"endowment":6.161207321695077,"self_citation_contribution":0.9241810982542616,"citation_network_contribution":0.0,"self_endowment_contribution":0.9241810982542616,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":473,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.047,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2015-02-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":29955,"name":"Konstantina Skourti-Stathaki","orcid":"0000-0002-1427-9757","position":1,"is_corresponding":false},{"id":29956,"name":"Steffen Ventz","orcid":"0000-0003-2229-9560","position":2,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":3,"is_corresponding":false},{"id":4558,"name":"Angela Yen","orcid":"0000-0002-9802-7679","position":4,"is_corresponding":false},{"id":29957,"name":"Kinga Kamieniarz-Gdula","orcid":"0000-0003-3789-5381","position":5,"is_corresponding":false},{"id":29958,"name":"Stoil Dimitrov","orcid":null,"position":6,"is_corresponding":false},{"id":29959,"name":"Shailja Pathania","orcid":"0000-0001-8974-6420","position":7,"is_corresponding":false},{"id":29960,"name":"Kristine M. McKinney","orcid":null,"position":8,"is_corresponding":false},{"id":772,"name":"Matthew L. Eaton","orcid":"0000-0002-3447-8059","position":9,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":10,"is_corresponding":false},{"id":29961,"name":"Sarah J. Hill","orcid":null,"position":11,"is_corresponding":false},{"id":2251,"name":"Giovanni Parmigiani","orcid":"0000-0002-8783-5961","position":12,"is_corresponding":false},{"id":29962,"name":"Nicholas J. Proudfoot","orcid":null,"position":13,"is_corresponding":false},{"id":447,"name":"David M. Livingston","orcid":"0000-0001-5765-6025","position":14,"is_corresponding":false},{"id":29963,"name":"Stoil D. Dimitrov","orcid":null,"position":15,"is_corresponding":false},{"id":29964,"name":"Kristine McKinney","orcid":null,"position":16,"is_corresponding":false},{"id":11020,"name":"Nicholas Proudfoot","orcid":"0000-0001-8646-3222","position":17,"is_corresponding":false},{"id":29954,"name":"Elodie Hatchi","orcid":"0000-0001-8494-9851","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}