{"doi":"10.1016/j.molcel.2023.12.039","title":"EXO1 protects BRCA1-deficient cells against toxic DNA lesions","abstract":"Inactivating mutations in the BRCA1 and BRCA2 genes impair DNA double-strand break (DSB) repair by homologous recombination (HR), leading to chromosomal instability and cancer. Importantly, BRCA1/2 deficiency also causes therapeutically targetable vulnerabilities. Here, we identify the dependency on the end resection factor EXO1 as a key vulnerability of BRCA1-deficient cells. EXO1 deficiency generates poly(ADP-ribose)-decorated DNA lesions during S phase that associate with unresolved DSBs and genomic instability in BRCA1-deficient but not in wild-type or BRCA2-deficient cells. Our data indicate that BRCA1/EXO1 double-deficient cells accumulate DSBs due to impaired repair by single-strand annealing (SSA) on top of their HR defect. In contrast, BRCA2-deficient cells retain SSA activity in the absence of EXO1 and hence tolerate EXO1 loss. Consistent with a dependency on EXO1-mediated SSA, we find that BRCA1-mutated tumors show elevated EXO1 expression and increased SSA-associated genomic scars compared with BRCA1-proficient tumors. Overall, our findings uncover EXO1 as a promising therapeutic target for BRCA1-deficient tumors.","journal":"Molecular Cell","year":2024,"id":419568,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"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":1209544,"name":"Anne Schreuder","orcid":"0000-0002-2268-0735","position":1,"is_corresponding":false},{"id":621611,"name":"Raphael Pavani","orcid":"0000-0002-7187-2995","position":2,"is_corresponding":false},{"id":1168884,"name":"Veronica Garzero","orcid":null,"position":3,"is_corresponding":false},{"id":1209545,"name":"Sidrit Uruci","orcid":"0000-0003-3248-7960","position":4,"is_corresponding":false},{"id":284786,"name":"Tiemen J. Wendel","orcid":"0009-0006-1434-2396","position":5,"is_corresponding":false},{"id":218117,"name":"Arne van Hoeck","orcid":"0000-0002-6570-1452","position":6,"is_corresponding":false},{"id":1168574,"name":"Marta San Martín Alonso","orcid":"0000-0001-9781-864X","position":7,"is_corresponding":false},{"id":1210300,"name":"Marieke Everts","orcid":null,"position":8,"is_corresponding":false},{"id":1168885,"name":"Dana Koerse","orcid":null,"position":9,"is_corresponding":false},{"id":246622,"name":"Elsa Callén","orcid":"0000-0002-6325-0221","position":10,"is_corresponding":false},{"id":934995,"name":"J. H. VAN BOOM","orcid":"0000-0001-5845-5364","position":11,"is_corresponding":false},{"id":15035,"name":"Hailiang Mei","orcid":"0000-0003-1781-5508","position":12,"is_corresponding":false},{"id":48139,"name":"Edwin Cuppen","orcid":"0000-0002-0400-9542","position":13,"is_corresponding":false},{"id":251361,"name":"Martijn S. Luijsterburg","orcid":"0000-0001-5796-6541","position":14,"is_corresponding":false},{"id":1209546,"name":"Marcel A.T.M. van Vugt","orcid":"0000-0002-3202-4678","position":15,"is_corresponding":false},{"id":248586,"name":"André Nussenzweig","orcid":null,"position":16,"is_corresponding":false},{"id":74281,"name":"Haico van Attikum","orcid":"0000-0001-8590-0240","position":17,"is_corresponding":false},{"id":1168576,"name":"Sylvie M. Noordermeer","orcid":"0000-0003-2737-9690","position":18,"is_corresponding":false},{"id":1168573,"name":"Bert van de Kooij","orcid":"0000-0003-1042-8409","position":0,"is_corresponding":true}],"reference_count":125,"raw_metadata":null,"created_at":"2026-07-19T01:57:19.937291Z","pmid":"38266640","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":[]}