{"doi":"10.1002/jcp.27082","title":"Genistein‐induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells","abstract":"Genistein (GES), a phytoestrogen, has potential chemopreventive and chemotherapeutic effects on cancer. The anticancer mechanism of GES may be related with topoisomerase II associated DNA double‐strand breaks (DSBs). However, the precise molecular mechanism remains elusive. Here, we performed genetic analyses using human lymphoblastoid TK6 cell lines to investigate whether non‐homologous DNA end joining (NHEJ) and homologous recombination (HR), the two major repair pathways of DSBs, were involved in repairing GES‐induced DNA damage. Our results showed that GES induced DSBs in TK6 cells. Cells lacking Ligase4, an NHEJ enzyme, are hypersensitive to GES. Furthermore, the sensitivity of Ligase4−/− cells was associated with enhanced DNA damage when comparing the accumulation of γ‐H2AX foci and number of chromosomal aberrations (CAs) with WT cells. In addition, cells lacking Rad54, a HR enzyme, also presented hypersensitivity and increased DNA damages in response to GES. Meanwhile, Treatment of GES‐lacking enhanced the accumulation of Rad51, an HR factor, in TK6 cells, especially in Ligase4−/−. These results provided direct evidence that GES induced DSBs in TK6 cells and clarified that both NHEJ and HR were involved in the repair of GES‐induced DNA damage, suggesting that GES in combination with inhibition of NHEJ or HR would provide a potential anticancer strategy.","journal":"Journal of Cellular Physiology","year":2019,"id":16403,"datarank":0.3936634413474676,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.048275677398360695,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.048275677398360695,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":7,"citers_with_citation_signal":5,"citers_with_endowment":5,"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":121175,"name":"Xiaohua Wu","orcid":null,"position":1,"is_corresponding":false},{"id":63573,"name":"Hao Liu","orcid":"0000-0002-8278-1263","position":2,"is_corresponding":false},{"id":121176,"name":"Ziyuan Cheng","orcid":null,"position":3,"is_corresponding":false},{"id":121177,"name":"Zilu Zhao","orcid":null,"position":4,"is_corresponding":false},{"id":121178,"name":"Cuifang Xiang","orcid":null,"position":5,"is_corresponding":false},{"id":121179,"name":"Xiaoyu Feng","orcid":null,"position":6,"is_corresponding":false},{"id":121180,"name":"Shunichi Takeda","orcid":null,"position":7,"is_corresponding":false},{"id":121181,"name":"Yong Qing","orcid":"0000-0002-0142-9752","position":8,"is_corresponding":false},{"id":121174,"name":"Xiaoqing Hu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30070703","pmcid":null,"openalex_id":"https://openalex.org/W2887418817","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81373431","title":null}],"total_grants":1,"fwci":0.2783,"citation_percentile":0.57494484,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcp.27082","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.27082","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jcp.27082","host_type":"publisher"},{"url":"https://doi.org/10.1002/jcp.27082","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30070703","host_type":"repository"}],"fields_of_study":["Cancer therapeutics and mechanisms","DNA Repair Mechanisms","Carcinogens and Genotoxicity Assessment","Chemistry","Medicine","Biology","Cell Cycle","Cell Line","DNA Breaks, Double-Stranded","DNA Damage","DNA End-Joining Repair","DNA Repair","DNA-Binding Proteins","Genistein","Homologous Recombination","Humans"],"mesh_terms":["Cell Cycle","Cell Line","DNA Damage","DNA Repair","DNA-Binding Proteins","Humans","Genistein","DNA Breaks, Double-Stranded","Homologous Recombination","DNA End-Joining Repair"],"keywords":["RAD51","Non-homologous end joining","Homologous recombination","DNA damage","DNA repair","Ku80","DNA repair protein XRCC4","DNA","Lymphoblast","Topoisomerase","Molecular biology","Biology","Cell biology","Chemistry","Cell culture","Genetics","Nucleotide excision repair","Gene","DNA-binding protein","Homologous Recombination (Hr)","Genistein (Ges)","Non-homologous Dna End Joining (Nhej)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T22:27:22.775188Z","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":[]}