{"doi":"10.1111/j.0105-2896.2004.00162.x","title":"The DNA‐dependent protein kinase: the director at the end","abstract":"<jats:p><jats:bold>Summary: </jats:bold> Efficient repair of DNA double‐strand breaks is essential for the maintenance of chromosomal integrity. In higher eukaryotes, non‐homologous end‐joining (NHEJ) DNA is the primary pathway that repairs these breaks. NHEJ also functions in developing lymphocytes to repair strand breaks that occur during V(D)J recombination, the site‐specific recombination process that provides for the assembly of functional antigen‐receptor genes. If V(D)J recombination is impaired, B‐ and T‐lymphocyte development is blocked resulting in severe combined immunodeficiency disease. In the last decade, an intensive research effort has focused on NHEJ resulting in a reasonable understanding of how double‐strand breaks are resolved. Six distinct gene products have been identified that function in this pathway (Ku70, Ku86, XRCC4, DNA ligase IV, Artemis, and DNA‐PKcs). Three of these comprise one complex, the DNA‐dependent protein kinase (DNA‐PK). This protein complex is central during NHEJ, because DNA‐PK initially recognizes and binds to the damaged DNA and then targets the other repair activities to the site of DNA damage. In this review, we discuss recent developments that have provided insight into how DNA‐PK functions, once bound to DNA ends.</jats:p>","journal":"Immunological Reviews","year":2004,"id":44374,"datarank":9.447831437343556,"base_score":5.3612921657094255,"endowment":5.3612921657094255,"self_citation_contribution":0.8041938248564139,"citation_network_contribution":8.643637612487142,"self_endowment_contribution":0.8041938248564139,"citer_contribution":8.643637612487142,"corpus_percentile":null,"corpus_rank":null,"citation_count":212,"citer_count":189,"citers_with_citation_signal":170,"citers_with_endowment":170,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":209020,"name":"Shikha Gupta","orcid":null,"position":1,"is_corresponding":false},{"id":209021,"name":"Dale A. Ramsden","orcid":null,"position":2,"is_corresponding":false},{"id":209022,"name":"Susan P. Lees‐Miller","orcid":null,"position":3,"is_corresponding":false},{"id":186630,"name":"Katheryn Meek","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.3612921657094255,"endowment":5.3612921657094255,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15242401","pmcid":null,"openalex_id":"https://openalex.org/W2096753300","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI32600","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI42938","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA084442","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA 84442-01","title":null}],"total_grants":4,"fwci":6.7526,"citation_percentile":0.97786473,"influential_citations":15,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":5},{"year":2014,"count":12},{"year":2015,"count":13},{"year":2016,"count":2},{"year":2017,"count":3},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":6},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":7},{"year":2024,"count":6},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.0105-2896.2004.00162.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.0105-2896.2004.00162.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.0105-2896.2004.00162.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15242401","host_type":"repository"}],"fields_of_study":["DNA Repair Mechanisms","CRISPR and Genetic Engineering","PARP inhibition in cancer therapy","Biology","Medicine","Animals","Antigens, Nuclear","DNA Repair","DNA-Activated Protein Kinase","DNA-Binding Proteins","Endonucleases","Gene Rearrangement, B-Lymphocyte","Gene Rearrangement, T-Lymphocyte","Humans","Ku Autoantigen","Matrix Attachment Regions","Nuclear Proteins","Phosphorylation","Protein Serine-Threonine Kinases"],"mesh_terms":["Ku Autoantigen","Animals","DNA Repair","DNA-Binding Proteins","Endonucleases","Humans","Nuclear Proteins","Phosphorylation","Gene Rearrangement, B-Lymphocyte","Gene Rearrangement, T-Lymphocyte","Protein Serine-Threonine Kinases","Antigens, Nuclear","Matrix Attachment Regions","DNA-Activated Protein Kinase"],"keywords":["Ku80","DNA repair protein XRCC4","Ku70","Non-homologous end joining","V(D)J recombination","DNA ligase","Biology","DNA repair","DNA","Replication protein A","Genetics","DNA-PKcs","Homologous recombination","Molecular biology","Gene","Cell biology","DNA mismatch repair","DNA-binding protein","Recombination","Transcription factor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-26T01:42:21.974311Z","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":[]}