{"doi":"10.1073/pnas.1010959107","title":"Rad52 inactivation is synthetically lethal with BRCA2 deficiency","abstract":"<jats:p>Synthetic lethality is a powerful approach to study selective cell killing based on genotype. We show that loss of Rad52 function is synthetically lethal with breast cancer 2, early onset (BRCA2) deficiency, whereas there was no impact on cell growth and viability in BRCA2-complemented cells. The frequency of both spontaneous and double-strand break-induced homologous recombination and ionizing radiation-induced Rad51 foci decreased by 2–10 times when Rad52 was depleted in BRCA2-deficient cells, with little to no effect in BRCA2-complemented cells. The absence of both Rad52 and BRCA2 resulted in extensive chromosome aberrations, especially chromatid-type aberrations. Ionizing radiation-induced and S phase-associated Rad52-Rad51 foci form equally well in the presence or absence of BRCA2, indicating that Rad52 can respond to DNA double-strand breaks and replication stalling independently of BRCA2. Rad52 thus is an independent and alternative repair pathway of homologous recombination and a target for therapy in BRCA2-deficient cells.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2011,"id":42035,"datarank":9.87845172326631,"base_score":5.834810737062605,"endowment":5.834810737062605,"self_citation_contribution":0.8752216105593909,"citation_network_contribution":9.003230112706918,"self_endowment_contribution":0.8752216105593909,"citer_contribution":9.003230112706918,"corpus_percentile":null,"corpus_rank":null,"citation_count":341,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":6,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":201723,"name":"Shaun P. Scott","orcid":null,"position":1,"is_corresponding":false},{"id":201724,"name":"Wendy Bussen","orcid":null,"position":2,"is_corresponding":false},{"id":201725,"name":"Girdhar G. Sharma","orcid":null,"position":3,"is_corresponding":false},{"id":201726,"name":"Gongshe Guo","orcid":null,"position":4,"is_corresponding":false},{"id":201727,"name":"Tej K. Pandita","orcid":null,"position":5,"is_corresponding":false},{"id":201728,"name":"Simon N. Powell","orcid":null,"position":6,"is_corresponding":false},{"id":201722,"name":"Zhihui Feng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.834810737062605,"endowment":5.834810737062605,"datacite_reuse_total":6,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21148102","pmcid":"PMC3021033","openalex_id":"https://openalex.org/W2014091491","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA107640","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA123232","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA123232","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA107640","title":null}],"total_grants":4,"fwci":6.943,"citation_percentile":0.9775723,"influential_citations":38,"citation_trend":[{"year":2012,"count":17},{"year":2013,"count":18},{"year":2014,"count":13},{"year":2015,"count":22},{"year":2016,"count":20},{"year":2017,"count":26},{"year":2018,"count":29},{"year":2019,"count":19},{"year":2020,"count":28},{"year":2021,"count":42},{"year":2022,"count":26},{"year":2023,"count":30},{"year":2024,"count":14},{"year":2025,"count":16},{"year":2026,"count":5}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.1010959107","host_type":"journal"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.1010959107","host_type":"GREEN"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.1010959107","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1010959107","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1010959107","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21148102","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3021033","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","PARP inhibition in cancer therapy","Biology","Medicine","BRCA2 Protein","Cell Line, Tumor","Cell Nucleus","Chromosomal Instability","Chromosome Aberrations","DNA Damage","Gene Expression Regulation, Neoplastic","Genetic Complementation Test","HeLa Cells","Humans","Microscopy, Fluorescence","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","Tetrazolium Salts","Thiazoles"],"mesh_terms":["Cell Nucleus","Chromosome Aberrations","DNA Damage","Genetic Complementation Test","HeLa Cells","Humans","Microscopy, Fluorescence","Tetrazolium Salts","Thiazoles","Gene Expression Regulation, Neoplastic","BRCA2 Protein","Chromosomal Instability","Cell Line, Tumor","Rad51 Recombinase","Rad52 DNA Repair and Recombination Protein","Hela Cells"],"keywords":["RAD52","RAD51","Homologous recombination","DNA repair","Biology","Homologous chromosome","BRCA2 Protein","DNA damage","Synthetic lethality","Genetics","DNA","Cell biology","Cancer research","Molecular biology","Mutation","Germline mutation","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.17037516.v1","title":"Additional file 1 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17037516","title":"Additional file 1 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17037522.v1","title":"Additional file 2 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17037522","title":"Additional file 2 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17037525.v1","title":"Additional file 3 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.17037525","title":"Additional file 3 of Nickel nanoparticle-induced cell transformation: involvement of DNA damage and DNA repair defect through HIF-1α/miR-210/Rad52 pathway","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-13T18:55:43.447042Z","pmid":null,"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":[]}