{"doi":"10.1038/s43018-024-00902-1","title":"Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability","abstract":null,"journal":"Nature Cancer","year":2025,"id":633278,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":1641807,"name":"Jillian Earley","orcid":null,"position":1,"is_corresponding":false},{"id":1034757,"name":"Christi A Wisniewski","orcid":"0000-0002-9984-5139","position":2,"is_corresponding":false},{"id":463288,"name":"Arthur M. Mercurio","orcid":"0000-0003-2762-7519","position":3,"is_corresponding":false},{"id":246228,"name":"Sharon B. Cantor","orcid":"0000-0003-2944-6156","position":4,"is_corresponding":false},{"id":1641806,"name":"Jenna M. Whalen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability","abstract":"Tumors lacking the BRCA1 and BRCA2 (BRCA) hereditary breast cancer genes display heightened sensitivity to anti-cancer treatments, such as inhibitors of poly (ADP-ribose) polymerase 1 (PARP1). However, when resistance develops, treatments are lacking. Using CRISPR technology, we discovered that enhancing homologous recombination through increased DNA end resection in BRCA1-deficient cells by loss of the 53BP1-Shieldin complex-which is associated with resistance to PARP inhibitors-also heightens sensitivity to DNA nicks. The sensitivity is caused by hyper-resection of nicks into extensive single-stranded regions that trigger cell death. Based on these findings and that nicks limit tumor formation in mice, we propose nickases as a tool for personalized medicine. Moreover, our findings indicate that restricting nick expansion is a critical function of the 53BP1-Shieldin complex.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39838098","pmcid":"PMC12041741","openalex_id":null,"authors":[],"funders":[{"funder_name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","grant_id":"R01 CA254037","title":null},{"funder_name":"U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute","grant_id":"1F32CA268524-01A1","title":"Mapping the BRCA2 replication gap suppression domain to uncover themolecular mechanism of chemotherapy response"},{"funder_name":"U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute","grant_id":"R01CA285607","title":null},{"funder_name":"NCI NIH HHS","grant_id":"F32 CA268524","title":null},{"funder_name":"NCI NIH HHS","grant_id":"F32 CA077880","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01CA285607-02","title":"Mechanisms and Therapy of Radiation Resistance in Breast Cancer"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA254037-03","title":"Defining BRCA replication dysfunction in therapy response"}],"total_grants":7,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"Springer Nature TDM","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12041741/pdf/nihms-2069638.pdf","host_type":"repository"},{"url":"https://www.nature.com/articles/s43018-024-00902-1.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s43018-024-00902-1","host_type":"publisher"},{"url":"https://doi.org/10.1038/s43018-024-00902-1","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/39838098","host_type":""}],"fields_of_study":["03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Cell Line, Tumor","Animals","Humans","Mice","Breast Neoplasms","DNA-Binding Proteins","BRCA1 Protein","Drug Resistance, Neoplasm","Female","Homologous Recombination","CRISPR-Cas Systems","Poly(ADP-ribose) Polymerase Inhibitors","Poly (ADP-Ribose) Polymerase-1","Tumor Suppressor p53-Binding Protein 1"],"keywords":["BRCA1 Protein","Poly (ADP-Ribose) Polymerase-1","Breast Neoplasms","Poly(ADP-ribose) Polymerase Inhibitors","DNA-Binding Proteins","Mice","Drug Resistance, Neoplasm","Cell Line, Tumor","Humans","Animals","Female","CRISPR-Cas Systems","Tumor Suppressor p53-Binding Protein 1","Homologous Recombination"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T11:42:29.129097Z","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":[]}