{"doi":"10.1073/pnas.0437964100","title":"Nonhomologous end joining and V(D)J recombination require an additional factor","abstract":"<jats:p>\n                    DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T\n                    <jats:sup>−</jats:sup>\n                    B\n                    <jats:sup>−</jats:sup>\n                    severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue in\n                    <jats:italic>Saccharomyces cerevisiae</jats:italic>\n                    functions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2003,"id":48024,"datarank":8.804902286926223,"base_score":5.236441962829949,"endowment":5.236441962829949,"self_citation_contribution":0.7854662944244925,"citation_network_contribution":8.01943599250173,"self_endowment_contribution":0.7854662944244925,"citer_contribution":8.01943599250173,"corpus_percentile":null,"corpus_rank":null,"citation_count":187,"citer_count":176,"citers_with_citation_signal":153,"citers_with_endowment":153,"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":224984,"name":"B. Kysela","orcid":null,"position":1,"is_corresponding":false},{"id":224985,"name":"L. A. Hanakahi","orcid":null,"position":2,"is_corresponding":false},{"id":224986,"name":"K. Manolis","orcid":null,"position":3,"is_corresponding":false},{"id":224987,"name":"E. Riballo","orcid":null,"position":4,"is_corresponding":false},{"id":224988,"name":"M. Stumm","orcid":null,"position":5,"is_corresponding":false},{"id":224989,"name":"T. O. Harville","orcid":null,"position":6,"is_corresponding":false},{"id":224990,"name":"S. C. West","orcid":null,"position":7,"is_corresponding":false},{"id":224991,"name":"M. A. Oettinger","orcid":null,"position":8,"is_corresponding":false},{"id":201062,"name":"P. A. Jeggo","orcid":null,"position":9,"is_corresponding":false},{"id":224983,"name":"Y. Dai","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nonhomologous end joining and V(D)J recombination require an additional factor","abstract":"<jats:p>\n                    DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T\n                    <jats:sup>−</jats:sup>\n                    B\n                    <jats:sup>−</jats:sup>\n                    severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue in\n                    <jats:italic>Saccharomyces cerevisiae</jats:italic>\n                    functions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.236441962829949,"endowment":5.236441962829949,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12604777","pmcid":"PMC151363","openalex_id":"https://openalex.org/W2059678690","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM58026","title":null}],"total_grants":1,"fwci":8.7798,"citation_percentile":0.98624448,"influential_citations":12,"citation_trend":[{"year":2012,"count":12},{"year":2013,"count":5},{"year":2014,"count":10},{"year":2015,"count":7},{"year":2016,"count":6},{"year":2017,"count":5},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0437964100","host_type":"journal"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0437964100","host_type":"BRONZE"},{"url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0437964100","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0437964100","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0437964100","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12604777","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/151363","host_type":"repository"},{"url":"https://research.birmingham.ac.uk/en/publications/ce10e3f5-bb72-4ad7-a58b-ccf9375e1eab","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","PARP inhibition in cancer therapy","Biology","Medicine","Animals","Catalytic Domain","Cells, Cultured","DNA Damage","DNA Ligase ATP","DNA Ligases","DNA Nucleotidyltransferases","DNA Repair","DNA, Complementary","DNA-Binding Proteins","Dose-Response Relationship, Radiation","Fibroblasts","Humans","Immunoblotting","Immunologic Deficiency Syndromes","Peptides","Protein Binding","Protein Structure, Tertiary","Reverse Transcriptase Polymerase Chain Reaction","Time Factors","Tumor Cells, Cultured","VDJ Recombinases"],"mesh_terms":["DNA Ligase ATP","Animals","Cells, Cultured","DNA Damage","DNA Nucleotidyltransferases","DNA Repair","DNA-Binding Proteins","Dose-Response Relationship, Radiation","Fibroblasts","Humans","Immunologic Deficiency Syndromes","Peptides","DNA Ligases","Protein Binding","Time Factors","Tumor Cells, Cultured","Immunoblotting","Protein Structure, Tertiary","DNA, Complementary","Reverse Transcriptase Polymerase Chain Reaction","Catalytic Domain","VDJ Recombinases"],"keywords":["Ku80","Non-homologous end joining","Ku70","V(D)J recombination","DNA repair protein XRCC4","DNA ligase","Biology","DNA repair","DNA","Genetics","Homologous recombination","RAG2","Molecular biology","Recombination","Cell biology","DNA-binding protein","DNA mismatch repair","Gene","Transcription factor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-18T20:21:44.656263Z","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":[]}