{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:10:09Z","timestamp":1790759409927,"version":"4.1.0"},"reference-count":195,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24390290, 15H02817, 20H04334, 25550024, 17K20042"],"award-info":[{"award-number":["24390290, 15H02817, 20H04334, 25550024, 17K20042"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The DNA-dependent protein kinase (DNA-PK) is composed of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku70\/Ku80 heterodimer. DNA-PK is thought to act as the \u201csensor\u201d for DNA double-stranded breaks (DSB), which are considered the most deleterious type of DNA damage. In particular, DNA-PKcs and Ku are shown to be essential for DSB repair through nonhomologous end joining (NHEJ). The phenotypes of animals and human individuals with defective DNA-PKcs or Ku functions indicate their essential roles in these developments, especially in neuronal and immune systems. DNA-PKcs are structurally related to Ataxia\u2013telangiectasia mutated (ATM), which is also implicated in the cellular responses to DSBs. DNA-PKcs and ATM constitute the phosphatidylinositol 3-kinase-like kinases (PIKKs) family with several other molecules. Here, we review the accumulated knowledge on the functions of DNA-PKcs, mainly based on the phenotypes of DNA-PKcs-deficient cells in animals and human individuals, and also discuss its relationship with ATM in the maintenance of genomic stability.<\/jats:p>","DOI":"10.3390\/genes12081143","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"1143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["DNA-Dependent Protein Kinase Catalytic Subunit: The Sensor for DNA Double-Strand Breaks Structurally and Functionally Related to Ataxia Telangiectasia Mutated"],"prefix":"10.3390","volume":"12","author":[{"given":"Yoshihisa","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anie Day D. C.","family":"Asa","sequence":"additional","affiliation":[{"name":"Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaity","family":"Modak","sequence":"additional","affiliation":[{"name":"Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Shimada","sequence":"additional","affiliation":[{"name":"Laboratory for Zero-Carbon Energy, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo 152-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/j.1460-2075.1985.tb02328.x","article-title":"Double-stranded DNA induces the phosphorylation of several proteins including the 90,000 mol. wt. heat-shock protein in animal cell extracts","volume":"4","author":"Walker","year":"1985","journal-title":"EMBO J."},{"key":"ref_2","first-page":"6460","article-title":"A DNA-activated protein kinase from HeLa cell nuclei","volume":"10","author":"Carter","year":"1990","journal-title":"Mol. 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