{"doi":"10.1016/j.celrep.2025.115654","title":"Distinct roles of the two BRCA2 DNA-binding domains in DNA damage repair and replication fork preservation","abstract":"Homologous recombination (HR) removes DNA double-strand breaks (DSBs) and preserves stressed DNA replication forks. Successful HR execution requires the tumor suppressor BRCA2, which harbors distinct DNA-binding domains (DBDs): one that possesses three oligonucleotide/oligosaccharide-binding (OB) folds (OB-DBD) and another residing in the C-terminal recombinase binding domain (CTRB-DBD). Here, we employ multi-faceted approaches to delineate the contributions of these domains toward HR and replication fork maintenance. We show that OB-DBD and CTRB-DBD confer single-strand DNA (ssDNA)- and dsDNA-binding capabilities, respectively, and that BRCA2 variants mutated in either domain are impaired in their ability to load the recombinase RAD51 onto ssDNA pre-occupied by RPA. While the CTRB-DBD mutant is modestly affected by DNA break repair, it exhibits a strong defect in the protection of stressed replication forks. In contrast, the OB-DBD is indispensable for both BRCA2 functions. Our study thus defines the unique contributions of the two BRCA2 DBDs in genome maintenance.","journal":"Cell Reports","year":2025,"id":523262,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":764373,"name":"Wenjing Li","orcid":"0000-0001-9151-9219","position":1,"is_corresponding":false},{"id":829314,"name":"Mollie E. Uhrig","orcid":"0000-0002-4142-8260","position":2,"is_corresponding":false},{"id":316890,"name":"Jeffrey N. Katz","orcid":"0000-0003-2104-4670","position":3,"is_corresponding":false},{"id":1277873,"name":"Shahrez Syed","orcid":null,"position":4,"is_corresponding":false},{"id":420172,"name":"Neelam Sharma","orcid":"0000-0003-0670-2188","position":5,"is_corresponding":false},{"id":685101,"name":"Arijit Dutta","orcid":"0000-0002-5675-0092","position":6,"is_corresponding":false},{"id":285265,"name":"Sandeep Burma","orcid":"0000-0001-7057-9845","position":7,"is_corresponding":false},{"id":240060,"name":"Robert Hromas","orcid":"0000-0002-1916-6276","position":8,"is_corresponding":false},{"id":459645,"name":"Alexander V. Mazin","orcid":"0000-0002-5430-9797","position":9,"is_corresponding":false},{"id":252086,"name":"Eloïse Dray","orcid":"0000-0001-6793-9838","position":10,"is_corresponding":false},{"id":825693,"name":"David S. Libich","orcid":"0000-0001-6492-2803","position":11,"is_corresponding":false},{"id":227437,"name":"Shaun K. Olsen","orcid":"0000-0002-1265-7101","position":12,"is_corresponding":false},{"id":328353,"name":"Elizabeth V. Wasmuth","orcid":"0000-0003-1474-4935","position":13,"is_corresponding":false},{"id":466236,"name":"Weixing Zhao","orcid":"0000-0001-5746-3696","position":14,"is_corresponding":false},{"id":863177,"name":"Claus Storgaard Sørensen","orcid":"0000-0001-6022-9710","position":15,"is_corresponding":false},{"id":466237,"name":"Claudia Wiese","orcid":"0000-0001-6844-4693","position":16,"is_corresponding":false},{"id":278335,"name":"Youngho Kwon","orcid":"0000-0002-0287-8795","position":17,"is_corresponding":false},{"id":278336,"name":"Patrick Sung","orcid":"0000-0003-1396-9040","position":18,"is_corresponding":false},{"id":1024255,"name":"Francisco Neal","orcid":"0000-0001-7676-8997","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40323719","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":[]}