{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRKDC encodes the catalytic subunit of DNA‐dependent protein kinase (DNA‐PKcs), a central orchestrator of the repair of DNA double‐strand breaks by nonhomologous end joining (NHEJ). DNA‐PKcs is rapidly recruited to damaged chromatin via its interaction with the Ku70/Ku80 heterodimer, where it forms a synaptic complex that bridges broken DNA ends. Subsequent autophosphorylation at key clusters—such as at Thr2609 and Ser2056 as well as additional sites—triggers conformational changes that regulate not only the stability of its association with DNA but also the accessibility for end processing. Detailed biochemical and structural studies (e.g., using single‐particle electron microscopy and crystallography) have revealed that these phosphorylation‐mediated conformational rearrangements of the DNA–PK complex are essential for coordinating proper DNA end joining and for influencing repair pathway choice."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n\nIn addition to its repair‐centric activities, DNA‐PKcs plays a multifaceted role in cellular signaling following DNA damage. It phosphorylates a variety of substrates—including Akt (at Ser473), histone H2AX, and tyrosyl‐DNA phosphodiesterase 1—thereby influencing cell survival pathways, chromatin remodeling, and the regulation of transcription. DNA‐PKcs also interacts with factors such as the epidermal growth factor receptor (EGFR), SIRT6, and regulatory phosphatases like PP6 to coordinate cell‐cycle checkpoint activation and to modulate translational reprogramming under genotoxic stress. Moreover, discrete autophosphorylation events have been implicated in the modulation of the interplay between NHEJ and homologous recombination, fine‐tuning the cellular decision‐making process during double‐strand break repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "29"}]}, {"type": "t", "text": "\n\nBeyond its canonical functions in DNA repair and damage signaling, aberrations in PRKDC have profound clinical and developmental implications. Mutations and subtle polymorphisms in DNA‐PKcs have been linked to immunodeficiency syndromes (such as radiosensitive severe combined immunodeficiency), predisposition to cancer, and treatment resistance—findings that underscore its influence on cellular survival and genomic stability. In addition, emerging evidence points to a critical requirement for DNA‐PKcs in human neurogenesis, with deficiencies leading to severe growth, cognitive, and structural brain abnormalities. These diverse roles, spanning genome surveillance to the regulation of transcription and cell fate, highlight PRKDC as a pivotal regulator of cellular homeostasis with broad implications in disease pathogenesis and therapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lisa G DeFazio, Rachel M Stansel, Jack D Griffith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synapsis of DNA ends by DNA-dependent protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdf299"}], "href": "https://doi.org/10.1093/emboj/cdf299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12065431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12065431"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Doug W Chan, Benjamin Ping-Chi Chen, Sheela Prithivirajsingh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1015202"}], "href": "https://doi.org/10.1101/gad.1015202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12231622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12231622"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dennis Merkle, Pauline Douglas, Greg B G Moorhead, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi0263558"}], "href": "https://doi.org/10.1021/bi0263558"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12379113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12379113"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qi Ding, Yeturu V R Reddy, Wei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.16.5836-5848.2003"}], "href": "https://doi.org/10.1128/MCB.23.16.5836-5848.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12897153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12897153"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jérôme Drouet, Christine Delteil, Jacques Lefrançois, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410746200"}], "href": "https://doi.org/10.1074/jbc.M410746200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15520013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15520013"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Benjamin P C Chen, Doug W Chan, Junya Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408827200"}], "href": "https://doi.org/10.1074/jbc.M408827200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15677476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15677476"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jacob Falck, Julia Coates, Stephen P Jackson "}, {"type": "b", "children": [{"type": "t", "text": "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature03442"}], "href": "https://doi.org/10.1038/nature03442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15758953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15758953"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yunmei Ma, Klaus Schwarz, Michael R Lieber "}, {"type": "b", "children": [{"type": "t", "text": "The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2005.04.013"}], "href": "https://doi.org/10.1016/j.dnarep.2005.04.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15936993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15936993"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Rémi Buisson, Jessica L Boisvert, Cyril H Benes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2015.07.029"}], "href": "https://doi.org/10.1016/j.molcel.2015.07.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26365377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26365377"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Thomas G W Graham, Johannes C Walter, Joseph J Loparo "}, {"type": "b", "children": [{"type": "t", "text": "Two-Stage Synapsis of DNA Ends during Non-homologous End Joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.02.010"}], "href": "https://doi.org/10.1016/j.molcel.2016.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26990988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26990988"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Bancinyane L Sibanda, Dimitri Y Chirgadze, David B Ascher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aak9654"}], "href": "https://doi.org/10.1126/science.aak9654"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28154079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28154079"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Eun-Jung Park, Doug W Chan, Ji-Hye Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkg921"}], "href": "https://doi.org/10.1093/nar/gkg921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14627815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14627815"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Suisheng Zhang, Bernhard Schlott, Matthias Görlach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkg933"}], "href": "https://doi.org/10.1093/nar/gkg933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14704337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14704337"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jianhua Feng, Jongsun Park, Peter Cron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406731200"}], "href": "https://doi.org/10.1074/jbc.M406731200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15262962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15262962"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Sandeep Burma, David J Chen "}, {"type": "b", "children": [{"type": "t", "text": "Role of DNA-PK in the cellular response to DNA double-strand breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2004.03.021"}], "href": "https://doi.org/10.1016/j.dnarep.2004.03.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15279776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15279776"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Hongyan Wang, Minli Wang, Huichen Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.20141"}], "href": "https://doi.org/10.1002/jcp.20141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15389585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15389585"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Klaus Dittmann, Claus Mayer, Birgit Fehrenbacher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M506591200"}], "href": "https://doi.org/10.1074/jbc.M506591200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16000298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16000298"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Aaron A Goodarzi, Yaping Yu, Enriqueta Riballo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PK autophosphorylation facilitates Artemis endonuclease activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601255"}], "href": "https://doi.org/10.1038/sj.emboj.7601255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16874298"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16874298"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Benjamin P C Chen, Naoya Uematsu, Junya Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M611605200"}], "href": "https://doi.org/10.1074/jbc.M611605200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17189255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17189255"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Mahmoud Toulany, Rainer Kehlbach, Urszula Florczak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-07-2200"}], "href": "https://doi.org/10.1158/1535-7163.MCT-07-2200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18644989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18644989"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Mirjam van der Burg, Hanna Ijspeert, Nicole S Verkaik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI37141"}], "href": "https://doi.org/10.1172/JCI37141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19075392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19075392"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Ian R Powley, Alexander Kondrashov, Lucy A Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translational reprogramming following UVB irradiation is mediated by DNA-PKcs and allows selective recruitment to the polysomes of mRNAs encoding DNA repair enzymes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.516509"}], "href": "https://doi.org/10.1101/gad.516509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19451221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19451221"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Benu Brata Das, Smitha Antony, Shalu Gupta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.302"}], "href": "https://doi.org/10.1038/emboj.2009.302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19851285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19851285"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Pauline Douglas, Jianing Zhong, Ruiqiong Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00741-09"}], "href": "https://doi.org/10.1128/MCB.00741-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20065038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20065038"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Jing An, Yue-Cheng Huang, Qing-Zhi Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2199-11-18"}], "href": "https://doi.org/10.1186/1471-2199-11-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20205745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20205745"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Michael D Kornberg, Nilkantha Sen, Makoto R Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GAPDH mediates nitrosylation of nuclear proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2114"}], "href": "https://doi.org/10.1038/ncb2114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20972425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20972425"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jessica A Neal, Van Dang, Pauline Douglas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01298-10"}], "href": "https://doi.org/10.1128/MCB.01298-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21300785"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21300785"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Tibor Pankotai, Céline Bonhomme, David Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2224"}], "href": "https://doi.org/10.1038/nsmb.2224"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22343725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22343725"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Suzette E Farber-Katz, Holly C Dippold, Matthew D Buschman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2013.12.023"}], "href": "https://doi.org/10.1016/j.cell.2013.12.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24485452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24485452"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Yi-Ping Fu, Jyh-Cherng Yu, Ting-Chih Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12750264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12750264"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Thomas Wechsler, Benjamin P C Chen, Ryan Harper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PKcs function regulated specifically by protein phosphatase 5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0307765100"}], "href": "https://doi.org/10.1073/pnas.0307765100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14734805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14734805"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Ganesh R Panta, Swayamjot Kaur, Lakita G Cavin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.5.1823-1835.2004"}], "href": "https://doi.org/10.1128/MCB.24.5.1823-1835.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14966265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14966265"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Li-E Wang, Melissa L Bondy, Hongbing Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms of DNA repair genes and risk of glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-03-2181"}], "href": "https://doi.org/10.1158/0008-5472.CAN-03-2181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15313891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15313891"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Elaine Huston, Martin J Lynch, Ahmed Mohamed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0805167105"}], "href": "https://doi.org/10.1073/pnas.0805167105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18728186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18728186"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Klaus Dittmann, Claus Mayer, Rainer Kehlbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-7-69"}], "href": "https://doi.org/10.1186/1476-4598-7-69"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18789131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18789131"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Euan A Stronach, Michelle Chen, Elaina N Maginn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.111032"}], "href": "https://doi.org/10.1593/neo.111032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22131882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22131882"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Anthony J Davis, Benjamin P C Chen, David J Chen "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PK: a dynamic enzyme in a versatile DSB repair pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2014.02.020"}], "href": "https://doi.org/10.1016/j.dnarep.2014.02.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24680878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24680878"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Nicholas Jette, Susan P Lees-Miller "}, {"type": "b", "children": [{"type": "t", "text": "The DNA-dependent protein kinase: A multifunctional protein kinase with roles in DNA double strand break repair and mitosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prog Biophys Mol Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pbiomolbio.2014.12.003"}], "href": "https://doi.org/10.1016/j.pbiomolbio.2014.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25550082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25550082"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Jonathan F Goodwin, Vishal Kothari, Justin M Drake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2015.06.004"}], "href": "https://doi.org/10.1016/j.ccell.2015.06.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26175416"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26175416"}]}]}]}