{"doi":"10.1101/2024.02.14.580374","title":"R-Loop Functions in <i>Brca1</i> -Associated Mammary Tumorigenesis","abstract":"Abstract Excessive R-loops, a DNA-RNA hybrid structure, are associated with genome instability and BRCA1 mutation-related breast cancer. Yet the causality of R-loops in tumorigenesis remains unclear. Here we show that R-loop removal by Rnaseh1 overexpression (Rh1-OE) in Brca1 -knockout (BKO) mouse mammary epithelium exacerbates DNA replication stress without affecting homology-directed DNA repair. R-loop removal also diminishes luminal progenitors, the cell of origin for estrogen receptor α (ERα)-negative BKO tumors. However, R-loop reduction does not dampen spontaneous BKO tumor incidence. Rather, it gives rise to a significant percentage of ERα-expressing BKO tumors. Thus, R-loops reshape mammary tumor subtype rather than promoting tumorigenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":494399,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":766248,"name":"Leilei Qi","orcid":null,"position":1,"is_corresponding":false},{"id":343244,"name":"Payal Mitra","orcid":null,"position":2,"is_corresponding":false},{"id":341854,"name":"Yanfen Hu","orcid":"0000-0001-9595-1631","position":3,"is_corresponding":false},{"id":440119,"name":"Rong Li","orcid":"0000-0003-3971-1670","position":4,"is_corresponding":false},{"id":341851,"name":"Huai-Chin Chiang","orcid":"0000-0002-7616-3362","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:09:11.736910Z","pmid":"38405919","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":[]}