{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:29:53Z","timestamp":1768505393875,"version":"3.49.0"},"posted":{"date-parts":[[2023,2,2]]},"group-title":"Molecular Biology","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Ataxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double strand breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PK\n                  <jats:sub>cs<\/jats:sub>\n                  ), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Phosphorylation at T4102 stabilizes the interaction between DNA-PK\n                  <jats:sub>cs<\/jats:sub>\n                  and the Ku-DNA complex and promotes assembly and stabilization of the NHEJ machinery at DSBs. Ablating phosphorylation at this site results in decreased NHEJ, radiosensitivity, and increased radiation-induced genomic instability. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PK\n                  <jats:sub>cs<\/jats:sub>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2023.02.02.526879","type":"posted-content","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:10:12Z","timestamp":1675383012000},"source":"Crossref","is-referenced-by-count":0,"title":["ATM phosphorylates the FATC domain of DNA-PK\n                  <sub>cs<\/sub>\n                  at threonine 4102 to promote non-homologous end joining"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2743-7419","authenticated-orcid":false,"given":"Huiming","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Laverty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Puncheon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary D.","family":"Nagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin PC","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony 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