{"doi":"10.1038/s41467-018-06435-3","title":"Spatiotemporal dynamics of homologous recombination repair at single collapsed replication forks","abstract":"<jats:title>Abstract</jats:title><jats:p>Homologous recombination (HR) is a crucial pathway for the repair of DNA double-strand breaks. BRCA1/2 breast cancer proteins are key players in HR via their mediation of RAD51 nucleofilament formation and function; however, their individual roles and crosstalk in vivo are unknown. Here we use super-resolution (SR) imaging to map the spatiotemporal kinetics of HR proteins, revealing the interdependent relationships that govern the dynamic interplay and progression of repair events. We show that initial single-stranded DNA/RAD51 nucleofilament formation is mediated by RAD52 or, in the absence of RAD52, by BRCA2. In contrast, only BRCA2 can orchestrate later RAD51 recombinase activity during homology search and resolution. Furthermore, we establish that upstream BRCA1 activity is critical for BRCA2 function. Our analyses reveal the underlying epistatic landscape of RAD51 functional dependence on RAD52, BRCA1, and BRCA2 during HR and explain the phenotypic similarity of diseases associated with mutations in these proteins.</jats:p>","journal":"Nature Communications","year":2018,"id":42074,"datarank":1.6465849261441377,"base_score":4.110873864173311,"endowment":4.110873864173311,"self_citation_contribution":0.6166310796259968,"citation_network_contribution":1.0299538465181408,"self_endowment_contribution":0.6166310796259968,"citer_contribution":1.0299538465181408,"corpus_percentile":null,"corpus_rank":null,"citation_count":60,"citer_count":39,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":67.5,"fair_percentile":96.41600703605981,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":201874,"name":"Wei Ting C. 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Whelan","orcid":"0000-0002-7078-5443","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.110873864173311,"endowment":4.110873864173311,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30250272","pmcid":"PMC6155164","openalex_id":"https://openalex.org/W2890864694","authors":[],"funders":[{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","grant_id":"GM108119","title":null},{"funder_name":"American Cancer Society","grant_id":"DMC-16-241-01","title":null},{"funder_name":"V Foundation for Cancer Research","grant_id":"D2018-020","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM108119","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001445","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM108119-04","title":"Single-Molecule 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Repair Mechanisms","Mitochondrial Function and Pathology","Carcinogens and Genotoxicity Assessment","Biology","Medicine","0301 basic medicine","0303 health sciences","03 medical and health sciences","BRCA1 Protein","BRCA2 Protein","Cell Line, Tumor","DNA Breaks, Double-Stranded","DNA, Single-Stranded","Gene Knockdown Techniques","Humans","Image Processing, Computer-Assisted","Microscopy, Fluorescence","RNA, Small Interfering","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","Recombinational DNA Repair","Single Molecule Imaging"],"mesh_terms":["Single Molecule Imaging","DNA, Single-Stranded","Humans","Image Processing, Computer-Assisted","Microscopy, Fluorescence","BRCA1 Protein","BRCA2 Protein","RNA, Small Interfering","Cell Line, Tumor","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","DNA Breaks, Double-Stranded","Gene Knockdown Techniques","Recombinational DNA Repair"],"keywords":["Homologous recombination","Homologous chromosome","Recombination","Replication (statistics)","Biology","Genetics","Cell biology","Computational biology","DNA","Gene","Virology","BRCA2 Protein","BRCA1 Protein","Science","Q","DNA, Single-Stranded","Recombinational DNA Repair","Article","Single Molecule Imaging","Rad52 DNA Repair and Recombination Protein","Microscopy, Fluorescence","Cell Line, Tumor","Gene Knockdown Techniques","Image Processing, Computer-Assisted","Humans","DNA Breaks, Double-Stranded","Rad51 Recombinase","RNA, Small Interfering"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and 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