{"doi":"10.1016/j.celrep.2021.108921","title":"SIRT2 promotes BRCA1-BARD1 heterodimerization through deacetylation","abstract":"The breast cancer type I susceptibility protein (BRCA1) and BRCA1-associated RING domain protein I (BARD1) heterodimer promote genome integrity through pleiotropic functions, including DNA double-strand break (DSB) repair by homologous recombination (HR). BRCA1-BARD1 heterodimerization is required for their mutual stability, HR function, and role in tumor suppression; however, the upstream signaling events governing BRCA1-BARD1 heterodimerization are unclear. Here, we show that SIRT2, a sirtuin deacetylase and breast tumor suppressor, promotes BRCA1-BARD1 heterodimerization through deacetylation. SIRT2 complexes with BRCA1-BARD1 and deacetylates conserved lysines in the BARD1 RING domain, interfacing BRCA1, which promotes BRCA1-BARD1 heterodimerization and consequently BRCA1-BARD1 stability, nuclear retention, and localization to DNA damage sites, thus contributing to efficient HR. Our findings define a mechanism for regulation of BRCA1-BARD1 heterodimerization through SIRT2 deacetylation, elucidating a critical upstream signaling event directing BRCA1-BARD1 heterodimerization, which facilitates HR and tumor suppression, and delineating a role for SIRT2 in directing DSB repair by HR.","journal":"Cell Reports","year":2021,"id":166657,"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":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":324907,"name":"Priya Kapoor-Vazirani","orcid":null,"position":1,"is_corresponding":false},{"id":692513,"name":"Chunyang Li","orcid":"0000-0002-1151-4897","position":2,"is_corresponding":false},{"id":251726,"name":"Hui Zhang","orcid":"0000-0001-6171-4785","position":3,"is_corresponding":false},{"id":693197,"name":"Kamakshi Balakrishnan","orcid":null,"position":4,"is_corresponding":false},{"id":323946,"name":"David S. Yu","orcid":"0000-0002-2781-5379","position":5,"is_corresponding":false},{"id":323937,"name":"Elizabeth V. Minten","orcid":"0000-0002-2078-2383","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T23:45:49.644768Z","pmid":"33789098","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":[]}