{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu Y"],"funding":["HHS | National Institutes of Health","HHS | NIH | National Cancer Institute","NCI NIH HHS"],"pagination":["e2221894120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10288554"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(25)"],"pubmed_abstract":["The nonhomologous end-joining (NHEJ) pathway is a major DNA double-strand break repair pathway in mammals and is essential for lymphocyte development. Ku70 and Ku80 heterodimer (KU) initiates NHEJ, thereby recruiting and activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). While DNA-PKcs deletion only moderately impairs end-ligation, the expression of kinase-dead DNA-PKcs completely abrogates NHEJ. Active DNA-PK phosphorylates DNA-PKcs at two clusters-PQR around S2056 (S2053 in mouse) and ABCDE around T2609. Alanine substitution at the S2056 cluster moderately compromises end-ligation on plasmid-based assays. But, mice carrying alanine substitution at all five serine residues within the S2056 cluster (<i>DNA-PKcs<sup>PQR/PQR</sup></i>) display no defect in lymphocyt"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice."],"pmcid":["PMC10288554"],"funding_grant_id":["P01 CA174653","R01 CA275184","P01CA174653","R01 CA158073","5R01CA158073","R01CA275184","P30 CA013696"],"pubmed_authors":["Lee BJ","Zha S","Zhu Y","Jiang W","Li A","Gershik S"],"additional_accession":[]},"is_claimable":false,"name":"Phosphorylation of DNA-PKcs at the S2056 cluster ensures efficient and productive lymphocyte development in XLF-deficient mice.","description":"The nonhomologous end-joining (NHEJ) pathway is a major DNA double-strand break repair pathway in mammals and is essential for lymphocyte development. Ku70 and Ku80 heterodimer (KU) initiates NHEJ, thereby recruiting and activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). While DNA-PKcs deletion only moderately impairs end-ligation, the expression of kinase-dead DNA-PKcs completely abrogates NHEJ. Active DNA-PK phosphorylates DNA-PKcs at two clusters-PQR around S2056 (S2053 in mouse) and ABCDE around T2609. Alanine substitution at the S2056 cluster moderately compromises end-ligation on plasmid-based assays. But, mice carrying alanine substitution at all five serine residues within the S2056 cluster (<i>DNA-PKcs<sup>PQR/PQR</sup></i>) display no defect in lymphocyt","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jun","modification":"2026-07-14T21:56:24.704Z","creation":"2025-07-06T03:04:28.74Z"},"accession":"S-EPMC10288554","cross_references":{"pubmed":["37307443"],"doi":["10.1073/pnas.2221894120"]}}