{"doi":"10.1093/nar/gkr656","title":"Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks","abstract":null,"journal":"Nucleic Acids Research","year":2011,"id":637096,"datarank":0.7117398192544876,"base_score":4.74493212836325,"endowment":4.74493212836325,"self_citation_contribution":0.7117398192544876,"citation_network_contribution":0.0,"self_endowment_contribution":0.7117398192544876,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":114,"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":1654021,"name":"Nadia Barboule","orcid":null,"position":1,"is_corresponding":false},{"id":1240399,"name":"Philippe Frit","orcid":"0000-0002-6571-8860","position":2,"is_corresponding":false},{"id":1654022,"name":"Dennis Gomez","orcid":null,"position":3,"is_corresponding":false},{"id":1654023,"name":"Oriane Bombarde","orcid":null,"position":4,"is_corresponding":false},{"id":1654024,"name":"Bettina Couderc","orcid":null,"position":5,"is_corresponding":false},{"id":1654025,"name":"Guo-Sheng Ren","orcid":null,"position":6,"is_corresponding":false},{"id":189228,"name":"Bernard Salles","orcid":null,"position":7,"is_corresponding":false},{"id":189229,"name":"Patrick Calsou","orcid":"0000-0001-7951-9806","position":8,"is_corresponding":false},{"id":1403156,"name":"Qiao Cheng","orcid":"0000-0002-1164-0877","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks","abstract":"In mammalian cells, the main pathway for DNA double-strand breaks (DSBs) repair is classical non-homologous end joining (C-NHEJ). An alternative or back-up NHEJ (B-NHEJ) pathway has emerged which operates preferentially under C-NHEJ defective conditions. Although B-NHEJ appears particularly relevant to genomic instability associated with cancer, its components and regulation are still largely unknown. To get insights into this pathway, we have knocked-down Ku, the main contributor to C-NHEJ. Thus, models of human cell lines have been engineered in which the expression of Ku70/80 heterodimer can be significantly lowered by the conditional induction of a shRNA against Ku70. On Ku reduction in cells, resulting NHEJ competent protein extracts showed a shift from C- to B-NHEJ that could be reversed by addition of purified Ku protein. Using a cellular fractionation protocol after treatment with a strong DSBs inducer followed by western blotting or immunostaining, we established that, among C-NHEJ factors, Ku is the main counteracting factor against mobilization of PARP1 and the MRN complex to damaged chromatin. In addition, Ku limits PAR synthesis and single-stranded DNA production in response to DSBs. These data support the involvement of PARP1 and the MRN proteins in the B-NHEJ route for the repair of DNA DSBs.","is_dataset_classified":null,"base_score":4.74493212836325,"endowment":4.74493212836325,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21880593","pmcid":"PMC3239177","openalex_id":"https://openalex.org/W2097457790","authors":[],"funders":[],"total_grants":0,"fwci":4.3794,"citation_percentile":0.9563493,"influential_citations":0,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":14},{"year":2014,"count":13},{"year":2015,"count":13},{"year":2016,"count":15},{"year":2017,"count":2},{"year":2018,"count":7},{"year":2019,"count":2},{"year":2020,"count":10},{"year":2021,"count":6},{"year":2022,"count":4},{"year":2023,"count":9},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/nar/article-pdf/39/22/9605/16779032/gkr656.pdf","host_type":"journal"},{"url":"https://academic.oup.com/nar/article-pdf/39/22/9605/16779032/gkr656.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/nar/article-pdf/39/22/9605/16779032/gkr656.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/nar/gkr656","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21880593","host_type":"repository"},{"url":"https://hal.inrae.fr/hal-02652710","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3239177","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3239177","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3239177?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["DNA Repair Mechanisms","PARP inhibition in cancer therapy","Nuclear Structure and Function","Antigens, Nuclear","Cell Fractionation","Cell Line","Chromatin","DNA Breaks, Double-Stranded","DNA End-Joining Repair","DNA-Binding Proteins","Gene Knockdown Techniques","Humans","Ku Autoantigen","Poly (ADP-Ribose) Polymerase-1","Poly(ADP-ribose) Polymerase Inhibitors","Poly(ADP-ribose) Polymerases"],"mesh_terms":["Poly(ADP-ribose) Polymerase Inhibitors","Poly (ADP-Ribose) Polymerase-1","Ku Autoantigen","Cell Fractionation","Cell Line","Chromatin","DNA-Binding Proteins","Humans","Poly(ADP-ribose) Polymerases","Antigens, Nuclear","DNA Breaks, Double-Stranded","Gene Knockdown Techniques","DNA End-Joining Repair"],"keywords":["Ku70","Ku80","Biology","Chromatin","PARP1","Molecular biology","Genome instability","Non-homologous end joining","DNA repair","DNA damage","Cell biology","DNA","Poly ADP ribose polymerase","Genetics","Transcription factor","DNA-binding protein","Gene","Polymerase"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T18:18:11.090013Z","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":[]}