{"doi":"10.1371/journal.pgen.1000855","title":"Ku Regulates the Non-Homologous End Joining Pathway Choice of DNA Double-Strand Break Repair in Human Somatic Cells","abstract":null,"journal":"PLoS Genetics","year":2010,"id":599367,"datarank":0.8245752337939805,"base_score":5.497168225293202,"endowment":5.497168225293202,"self_citation_contribution":0.8245752337939805,"citation_network_contribution":0.0,"self_endowment_contribution":0.8245752337939805,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":243,"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":1536093,"name":"Eu Han Lee","orcid":null,"position":1,"is_corresponding":false},{"id":1536094,"name":"Natalie Weisensel","orcid":null,"position":2,"is_corresponding":false},{"id":1536095,"name":"Yongbao Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1536096,"name":"Natalie Lichter","orcid":null,"position":4,"is_corresponding":false},{"id":365949,"name":"Eric A. Hendrickson","orcid":"0000-0001-6734-6426","position":5,"is_corresponding":false},{"id":285261,"name":"Farjana Fattah","orcid":"0000-0002-7897-2788","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ku Regulates the Non-Homologous End Joining Pathway Choice of DNA Double-Strand Break Repair in Human Somatic Cells","abstract":"The repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or \"classic\" NHEJ (C-NHEJ) pathway and an \"alternative\" NHEJ (A-NHEJ) pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs), XLF, and LIGIV), and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs), XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs)-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.","is_dataset_classified":null,"base_score":5.497168225293202,"endowment":5.497168225293202,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20195511","pmcid":"PMC2829059","openalex_id":"https://openalex.org/W1995920076","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM069576","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA77598","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA077598","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL079559","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL079559","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM069576","title":null},{"funder_name":"NIA NIH HHS","grant_id":"T32 AG029796","title":null},{"funder_name":"National Institutes of Health","grant_id":"5P30CA077598-08","title":"Cancer Center Support Grant P30 CA77598-06"}],"total_grants":8,"fwci":10.5784,"citation_percentile":0.99019821,"influential_citations":0,"citation_trend":[{"year":2012,"count":27},{"year":2013,"count":29},{"year":2014,"count":26},{"year":2015,"count":27},{"year":2016,"count":20},{"year":2017,"count":16},{"year":2018,"count":8},{"year":2019,"count":11},{"year":2020,"count":7},{"year":2021,"count":11},{"year":2022,"count":6},{"year":2023,"count":9},{"year":2024,"count":6},{"year":2025,"count":4},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000855&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000855&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pgen.1000855","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pgen.1000855","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20195511","host_type":"repository"},{"url":"https://doaj.org/article/210d85442b3a4b30b881cb2c5e98cba2","host_type":"repository"},{"url":"https://figshare.com/articles/Ku_Regulates_the_Non_Homologous_End_Joining_Pathway_Choice_of_DNA_Double_Strand_Break_Repair_in_Human_Somatic_Cells/144587","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2829059","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2829059","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2829059?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pgen.1000855","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pgen.1000855","host_type":""}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","PARP inhibition in cancer therapy","0301 basic medicine","03 medical and health sciences","0303 health sciences","Animals","Cricetinae","DNA","DNA Breaks, Double-Stranded","DNA Helicases","DNA Ligase ATP","DNA Ligases","DNA Repair","DNA Repair Enzymes","DNA-Activated Protein Kinase","DNA-Binding Proteins","HCT116 Cells","Haploidy","Humans","Ku Autoantigen","Mutation","Nuclear Proteins","Plasmids","Recombination, Genetic","Reproducibility of Results"],"mesh_terms":["Ku Autoantigen","DNA Ligase ATP","Animals","DNA","DNA Repair","DNA Helicases","DNA-Binding Proteins","Cricetinae","Haploidy","Humans","Mutation","Nuclear Proteins","Plasmids","DNA Ligases","Recombination, Genetic","Reproducibility of Results","HCT116 Cells","DNA Repair Enzymes","DNA-Activated Protein Kinase","DNA Breaks, Double-Stranded"],"keywords":["Ku80","Non-homologous end joining","Ku70","Biology","DNA repair protein XRCC4","DNA repair","Homologous recombination","Homology directed repair","DNA damage","Somatic cell","Cell biology","DNA","Molecular biology","Genetics","Gene","Nucleotide excision repair","DNA-binding protein","Transcription factor","DNA Ligases","DNA-Activated Protein Kinase","QH426-470","Haploidy","DNA Ligase ATP","Cricetinae","Animals","Humans","DNA Breaks, Double-Stranded","Ku Autoantigen","Recombination, Genetic","DNA Helicases","Nuclear Proteins","Reproducibility of Results","HCT116 Cells","DNA-Binding Proteins","DNA Repair Enzymes","Mutation","Research Article","Plasmids"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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