{"doi":"10.1073/pnas.052545899","title":"DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination","abstract":"<jats:p>\n                    DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in repairing double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). Certain proteins involved in NHEJ are also involved in DSB repair by homologous recombination (HR). To test the effects of DNA-PKcs on DSB-induced HR, we integrated\n                    <jats:italic>neo</jats:italic>\n                    direct repeat HR substrates carrying the I\n                    <jats:italic>-Sce</jats:italic>\n                    I recognition sequence into DNA-PKcs-defective Chinese hamster ovary (V3) cells. The DNA-PKcs defect was complemented with a human DNA-PKcs cDNA. DSB-induced HR frequencies were 1.5- to 3-fold lower with DNA-PKcs complementation. In complemented and uncomplemented strains, all products arose by gene conversion without associated crossover, and average conversion tract lengths were similar. Suppression of DSB-induced HR in complemented cells probably reflects restoration of NHEJ, consistent with competition between HR and NHEJ during DSB repair. Interestingly, spontaneous HR rates were 1.6- to &gt;3.5-fold lower with DNA-PKcs complementation. DNA-PKcs may suppress spontaneous HR through NHEJ of spontaneous DSBs, perhaps at stalled or blocked replication forks. Because replication protein A (RPA) is involved in both replication and HR, and is phosphorylated by DNA-PKcs, it is possible that the suppression of spontaneous HR by DNA-PKcs reflects regulation of replication-dependent HR by DNA-PKcs, perhaps by means of phosphorylation of RPA.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2002,"id":658199,"datarank":7.516800581373303,"base_score":5.214935757608986,"endowment":5.214935757608986,"self_citation_contribution":0.782240363641348,"citation_network_contribution":6.734560217731955,"self_endowment_contribution":0.782240363641348,"citer_contribution":6.734560217731955,"corpus_percentile":null,"corpus_rank":null,"citation_count":183,"citer_count":151,"citers_with_citation_signal":134,"citers_with_endowment":134,"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":1718199,"name":"Akihiro Kurimasa","orcid":null,"position":1,"is_corresponding":false},{"id":1718200,"name":"Mark A. Brenneman","orcid":null,"position":2,"is_corresponding":false},{"id":597257,"name":"David J. Chen","orcid":"0000-0003-0046-6903","position":3,"is_corresponding":false},{"id":420176,"name":"Jac A. Nickoloff","orcid":"0000-0001-8606-7545","position":4,"is_corresponding":false},{"id":420173,"name":"Chris Allen","orcid":"0000-0003-3808-5209","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination","abstract":"<jats:p>\n                    DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in repairing double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). Certain proteins involved in NHEJ are also involved in DSB repair by homologous recombination (HR). To test the effects of DNA-PKcs on DSB-induced HR, we integrated\n                    <jats:italic>neo</jats:italic>\n                    direct repeat HR substrates carrying the I\n                    <jats:italic>-Sce</jats:italic>\n                    I recognition sequence into DNA-PKcs-defective Chinese hamster ovary (V3) cells. The DNA-PKcs defect was complemented with a human DNA-PKcs cDNA. DSB-induced HR frequencies were 1.5- to 3-fold lower with DNA-PKcs complementation. In complemented and uncomplemented strains, all products arose by gene conversion without associated crossover, and average conversion tract lengths were similar. Suppression of DSB-induced HR in complemented cells probably reflects restoration of NHEJ, consistent with competition between HR and NHEJ during DSB repair. Interestingly, spontaneous HR rates were 1.6- to &gt;3.5-fold lower with DNA-PKcs complementation. DNA-PKcs may suppress spontaneous HR through NHEJ of spontaneous DSBs, perhaps at stalled or blocked replication forks. Because replication protein A (RPA) is involved in both replication and HR, and is phosphorylated by DNA-PKcs, it is possible that the suppression of spontaneous HR by DNA-PKcs reflects regulation of replication-dependent HR by DNA-PKcs, perhaps by means of phosphorylation of RPA.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.214935757608986,"endowment":5.214935757608986,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11904432","pmcid":"PMC122597","openalex_id":"https://openalex.org/W2160532161","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA74046","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA77693","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA077693","title":null}],"total_grants":3,"fwci":5.3667,"citation_percentile":0.96720453,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":5},{"year":2014,"count":8},{"year":2015,"count":6},{"year":2016,"count":4},{"year":2017,"count":5},{"year":2019,"count":1},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2022,"count":21},{"year":2023,"count":6},{"year":2024,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122597","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/122597","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.052545899","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.052545899","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11904432","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","Photosynthetic Processes and Mechanisms"],"mesh_terms":["Animals","Cell Line","DNA","DNA Damage","DNA Repair","DNA Replication","DNA-Binding Proteins","Gene Conversion","Genetic Complementation Test","Cricetinae","Humans","Models, Genetic","Mutation","Neomycin","Nuclear Proteins","Recombination, Genetic","Repetitive Sequences, Nucleic Acid","Sequence Homology, Nucleic Acid","Blotting, Western","Protein Serine-Threonine Kinases","DNA-Activated Protein Kinase"],"keywords":["Ku80","Ku70","DNA-PKcs","Homologous recombination","Replication protein A","Non-homologous end joining","Molecular biology","Biology","DNA repair protein XRCC4","DNA repair","DNA replication","Chinese hamster ovary cell","DNA","RAD51","DNA ligase","Cell biology","DNA mismatch repair","Gene","DNA-binding protein","Genetics","Cell culture","Transcription factor","Non-programmatic"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T03:34:31.078692Z","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":[]}