{"doi":"10.1073/pnas.0708541104","title":"Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends","abstract":"<jats:p>\n                    XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we address whether this difference in phenotype is connected to nonhomologous end-joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal double-strand breaks (DSBs) targeted by I-SceI, in living cells. In\n                    <jats:italic>xrcc4</jats:italic>\n                    -defective XR-1 cells, a residual but significant end-joining process exists, which primarily uses microhomologies distal from the DSB. However, NHEJ efficiency was strongly reduced in\n                    <jats:italic>xrcc4</jats:italic>\n                    -defective XR-1 cells versus complemented cells, contrasting with KU-deficient xrs6 cells, which showed levels of end-joining similar to those of complemented cells. Nevertheless, sequence analysis of the repair junctions indicated that the accuracy of end-joining was strongly affected in both\n                    <jats:italic>xrcc4</jats:italic>\n                    -deficient and KU-deficient cells. More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2007,"id":46671,"datarank":6.912294648200519,"base_score":5.123963979403259,"endowment":5.123963979403259,"self_citation_contribution":0.7685945969104889,"citation_network_contribution":6.14370005129003,"self_endowment_contribution":0.7685945969104889,"citer_contribution":6.14370005129003,"corpus_percentile":null,"corpus_rank":null,"citation_count":167,"citer_count":143,"citers_with_citation_signal":132,"citers_with_endowment":132,"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":216062,"name":"Emilie Rass","orcid":"0000-0003-4890-7771","position":1,"is_corresponding":false},{"id":216063,"name":"Isabelle Plo","orcid":null,"position":2,"is_corresponding":false},{"id":216064,"name":"Pascale Bertrand","orcid":null,"position":3,"is_corresponding":false},{"id":202176,"name":"Bernard S. Lopez","orcid":"0000-0001-5088-0155","position":4,"is_corresponding":false},{"id":202166,"name":"Josée Guirouilh-Barbat","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends","abstract":"<jats:p>\n                    XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we address whether this difference in phenotype is connected to nonhomologous end-joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal double-strand breaks (DSBs) targeted by I-SceI, in living cells. In\n                    <jats:italic>xrcc4</jats:italic>\n                    -defective XR-1 cells, a residual but significant end-joining process exists, which primarily uses microhomologies distal from the DSB. However, NHEJ efficiency was strongly reduced in\n                    <jats:italic>xrcc4</jats:italic>\n                    -defective XR-1 cells versus complemented cells, contrasting with KU-deficient xrs6 cells, which showed levels of end-joining similar to those of complemented cells. Nevertheless, sequence analysis of the repair junctions indicated that the accuracy of end-joining was strongly affected in both\n                    <jats:italic>xrcc4</jats:italic>\n                    -deficient and KU-deficient cells. More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.123963979403259,"endowment":5.123963979403259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18093953","pmcid":"PMC2409239","openalex_id":"https://openalex.org/W1970347880","authors":[],"funders":[],"total_grants":0,"fwci":4.6633,"citation_percentile":0.95656305,"influential_citations":8,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":10},{"year":2014,"count":13},{"year":2015,"count":18},{"year":2016,"count":7},{"year":2017,"count":4},{"year":2018,"count":6},{"year":2019,"count":11},{"year":2020,"count":3},{"year":2021,"count":8},{"year":2022,"count":4},{"year":2023,"count":5},{"year":2024,"count":3},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2409239","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc2409239?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2409239","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0708541104","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0708541104","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18093953","host_type":"repository"},{"url":"https://hal.science/hal-03048190","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","Genomics and Chromatin Dynamics","Biology","Medicine","Animals","Antigens, Nuclear","CD4-Positive T-Lymphocytes","CHO Cells","Cricetinae","Cricetulus","DNA Damage","DNA Repair","DNA-Binding Proteins","Flow Cytometry","Gene Expression Regulation","Genetic Complementation Test","Ku Autoantigen","Mice","Mice, Transgenic","Models, Genetic","Phenotype"],"mesh_terms":["Ku Autoantigen","Animals","Cricetulus","DNA Damage","DNA Repair","DNA-Binding Proteins","Flow Cytometry","Gene Expression Regulation","Genetic Complementation Test","Cricetinae","Mice, Transgenic","Models, Genetic","Phenotype","CD4-Positive T-Lymphocytes","CHO Cells","Antigens, Nuclear","Mice"],"keywords":["Ku80","Non-homologous end joining","DNA repair protein XRCC4","Mutagenesis","Biology","Phenotype","Cell biology","Mutation","Genetics","Molecular biology","DNA repair","DNA","Gene","DNA-binding protein","DNA mismatch repair"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-13T00:59:18.317220Z","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":[]}