DNA-PKcs

Summary

Gene Symbol: DNA-PKcs
Description: protein kinase, DNA-activated, catalytic polypeptide
Alias: DNA-PKcs, DNAPK, DNPK1, HYRC, HYRC1, IMD26, XRCC7, p350, DNA-dependent protein kinase catalytic subunit, DNA-PK catalytic subunit, hyper-radiosensitivity of murine scid mutation, complementing 1, p460
Species: human
Products:     DNA-PKcs

Top Publications

  1. Teraoka H, Yumoto Y, Watanabe F, Tsukada K, Suwa A, Enari M, et al. CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme. FEBS Lett. 1996;393:1-6 pubmed
    DNA-dependent protein kinase (DNA-PK) is composed of a 460-kDa catalytic component (p460) and a DNA-binding component Ku protein...
  2. Chan D, Mody C, Ting N, Lees Miller S. Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta. Biochem Cell Biol. 1996;74:67-73 pubmed
    ..protein kinase (DNA-PK) is a serine-threonine protein kinase that is composed of a large catalytic subunit (p350) and a DNA-binding protein of 70 and 80 kDa subunits known as the Ku autoantigen...
  3. Povirk L, Zhou R, Ramsden D, Lees Miller S, Valerie K. Phosphorylation in the serine/threonine 2609-2647 cluster promotes but is not essential for DNA-dependent protein kinase-mediated nonhomologous end joining in human whole-cell extracts. Nucleic Acids Res. 2007;35:3869-78 pubmed
  4. Chen B, Chan D, Kobayashi J, Burma S, Asaithamby A, Morotomi Yano K, et al. Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J Biol Chem. 2005;280:14709-15 pubmed
    ..These results indicate that although IR-induced DNA-PKcs phosphorylation is attenuated in the S phase, DNA-PKcs is preferentially activated by the physiologically relevant DNA replication-associated DSBs at the sites of DNA synthesis. ..
  5. Sallmyr A, Miller A, Gabdoulkhakova A, Safronova V, Henriksson G, Bredberg A. Expression of DNA-dependent protein kinase in human granulocytes. Cell Res. 2004;14:331-40 pubmed
    ..In conclusion, our findings provide evidence of reduced, not depleted expression of DNA-PK during the mature stages of myeloid differentiation. ..
  6. Ting N, Kao P, Chan D, Lintott L, Lees Miller S. DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45. J Biol Chem. 1998;273:2136-45 pubmed
    ..Together, our data suggest that NF90, in complex with NF45, interacts with DNA-PKcs and Ku on DNA and that NF90 and NF45 may be important for the function of DNA-PK. ..
  7. Chen B, Uematsu N, Kobayashi J, Lerenthal Y, Krempler A, Yajima H, et al. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem. 2007;282:6582-7 pubmed
    ..Finally, our result provides a possible mechanism for the direct involvement of ATM in non-homologous end joining-mediated DSB repair. ..
  8. Malu S, De Ioannes P, Kozlov M, Greene M, Francis D, Hanna M, et al. Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs. J Exp Med. 2012;209:955-63 pubmed publisher
    ..Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs. ..
  9. Falck J, Coates J, Jackson S. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005;434:605-11 pubmed

More Information

Publications132 found, 100 shown here

  1. Daniel R, Katz R, Skalka A. A role for DNA-PK in retroviral DNA integration. Science. 1999;284:644-7 pubmed
    ..These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway. ..
  2. Hirata H, Hinoda Y, Tanaka Y, Okayama N, Suehiro Y, Kawamoto K, et al. Polymorphisms of DNA repair genes are risk factors for prostate cancer. Eur J Cancer. 2007;43:231-7 pubmed
    ..controls were analyzed by PCR-RFLP to determine the genotypic frequency of three DNA repair genes (XRCC1, XPC and XRCC7). We found that the frequency of 939Gln variant at XPC Lys939Gln was significantly lower in PC cases (OR=0.39, P=0...
  3. Douglas P, Sapkota G, Morrice N, Yu Y, Goodarzi A, Merkle D, et al. Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem J. 2002;368:243-51 pubmed
    ..Moreover, we show that DNA-PKcs is phosphorylated in vivo at Thr2609, Ser2612, Thr2638 and Thr2647 in okadaic acid-treated human cells. We propose that phosphorylation of these sites may play an important role in DNA-PK function. ..
  4. Hsu H, Yannone S, Chen D. Defining interactions between DNA-PK and ligase IV/XRCC4. DNA Repair (Amst). 2002;1:225-35 pubmed
    ..Our data defines the specific protein pairs involved in the association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for coordinating the assembly of the DNA repair complex at DNA breaks. ..
  5. Langland G, Yannone S, Langland R, Nakao A, Guan Y, Long S, et al. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities. Oncol Rep. 2010;23:1021-6 pubmed
    ..These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNA-PK in ovarian cancer. ..
  6. Rivera Calzada A, Maman J, Maman J, Spagnolo L, Pearl L, Llorca O. Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure. 2005;13:243-55 pubmed
    ..Comparison of DNA-PKcs with another PIKK DNA repair factor, ATM, defines a common architecture for this important protein family. ..
  7. Sarkaria J, Tibbetts R, Busby E, Kennedy A, Hill D, Abraham R. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res. 1998;58:4375-82 pubmed
    ..These results identify wortmannin as an inhibitor of ATM activity and suggest that ATM and DNA-PK are relevant targets for the radiosensitizing effect of this drug in cancer cells. ..
  8. Ma Y, Pannicke U, Schwarz K, Lieber M. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell. 2002;108:781-94 pubmed
  9. Medunjanin S, Weinert S, Poitz D, Schmeisser A, Strasser R, Braun Dullaeus R. Transcriptional activation of DNA-dependent protein kinase catalytic subunit gene expression by oestrogen receptor-alpha. EMBO Rep. 2010;11:208-13 pubmed publisher
    ..This previously unknown mechanism of DNA-PK regulation sheds new light on tumour biology and reveals new possibilities for the prevention and therapy of E2-sensitive proliferative diseases. ..
  10. Lee K, Lin Y, Chou H, Yajima H, Fattah K, Lee S, et al. Involvement of DNA-dependent protein kinase in normal cell cycle progression through mitosis. J Biol Chem. 2011;286:12796-802 pubmed publisher
    ..These results demonstrate for the first time that DNA-PKcs, in addition to its role in DSB repair, is a critical regulator of mitosis and could modulate microtubule dynamics in chromosome segregation. ..
  11. Yajima H, Lee K, Zhang S, Kobayashi J, Chen B. DNA double-strand break formation upon UV-induced replication stress activates ATM and DNA-PKcs kinases. J Mol Biol. 2009;385:800-10 pubmed publisher
    ..These results suggest that the late increase of ATM activity is needed to complement the decreasing ATR activity for maintaining a vigilant checkpoint regulation upon replication stress. ..
  12. Reichman T, Muniz L, Mathews M. The RNA binding protein nuclear factor 90 functions as both a positive and negative regulator of gene expression in mammalian cells. Mol Cell Biol. 2002;22:343-56 pubmed
    ..This report characterizes NF90 as both a positive and negative regulator of gene expression, depending on the promoter context, and suggests a role for NF45 as a regulator of NF90. ..
  13. Merkle D, Douglas P, Moorhead G, Leonenko Z, Yu Y, Cramb D, et al. The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation. Biochemistry. 2002;41:12706-14 pubmed
    ..We propose that autophosphorylation of DNA-PK plays an important regulatory role in DNA double-strand break repair by regulating the assembly and disassembly of the DNA-PK-DNA complex. ..
  14. Carter T, Vancurova I, Sun I, Lou W, DeLeon S. A DNA-activated protein kinase from HeLa cell nuclei. Mol Cell Biol. 1990;10:6460-71 pubmed
    ..These characteristics identify DNA-PK as distinct from other protein kinases described in the literature and suggest that activation by DNA is an important feature of the enzyme's in vivo function. ..
  15. Ju J, Naura A, Errami Y, Zerfaoui M, Kim H, Kim J, et al. Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment. J Biol Chem. 2010;285:41152-60 pubmed publisher
    ..Together, these results elucidate a novel mechanism for the involvement of DNA-PK in the positive regulation of p50 NF-?B to drive VCAM-1 expression. ..
  16. Niu H, Erdjument Bromage H, Pan Z, Lee S, Tempst P, Hurwitz J. Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro. J Biol Chem. 1997;272:12634-41 pubmed
    ..We also identified Ser-29 as the major Cdc2 kinase phosphorylation site in the p34 subunit. ..
  17. Giffin W, Kwast Welfeld J, Rodda D, Préfontaine G, Traykova Andonova M, Zhang Y, et al. Sequence-specific DNA binding and transcription factor phosphorylation by Ku Autoantigen/DNA-dependent protein kinase. Phosphorylation of Ser-527 of the rat glucocorticoid receptor. J Biol Chem. 1997;272:5647-58 pubmed
    ..This site occurs adjacent the GR nuclear localization sequence between the DNA and ligand binding domains of GR, and thus its phosphorylation, if confirmed, has the potential to affect receptor function in vivo. ..
  18. An J, Huang Y, Xu Q, Zhou L, Shang Z, Huang B, et al. DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression. BMC Mol Biol. 2010;11:18 pubmed publisher
    ..It can directly phosphorylate H2AX independent of ATM and indirectly modulate the phosphorylation level of gamma H2AX via the Akt/GSK3 beta signal pathway. ..
  19. Lees Miller S, Anderson C. The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues. J Biol Chem. 1989;264:17275-80 pubmed
    ..Mouse hsp86 and rabbit hsp90 alpha are homologous to human hsp90 alpha; both heterologous proteins are phosphorylated at the same amino-terminal threonines by the human dsDNA-activated protein kinase. ..
  20. Allen C, Kurimasa A, Brenneman M, Chen D, Nickoloff J. DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination. Proc Natl Acad Sci U S A. 2002;99:3758-63 pubmed
  21. Wong R, Chang I, Hudak C, Hyun S, Kwan H, Sul H. A role of DNA-PK for the metabolic gene regulation in response to insulin. Cell. 2009;136:1056-72 pubmed publisher
    ..Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation. ..
  22. Gell D, Jackson S. Mapping of protein-protein interactions within the DNA-dependent protein kinase complex. Nucleic Acids Res. 1999;27:3494-502 pubmed
    ..These data suggest that Ku has evolved to become part of the DNA-PK holo-enzyme by acquisition of a protein-protein interaction motif at the C-terminus of Ku80. ..
  23. Kumar S, Pandey P, Bharti A, Jin S, Weichselbaum R, Weaver D, et al. Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase. J Biol Chem. 1998;273:25654-8 pubmed
    ..These results support the hypothesis that there are functional interactions between Lyn and DNA-PKcs in the response to DNA damage. ..
  24. Sun Y, Huang Y, Xu Q, Wang H, Bai B, Sui J, et al. HIV-1 Tat depresses DNA-PK(CS) expression and DNA repair, and sensitizes cells to ionizing radiation. Int J Radiat Oncol Biol Phys. 2006;65:842-50 pubmed
    ..These observations provide new insight into the increased tissue reactions of AIDS cancer patients to radiotherapy. ..
  25. Dragoi A, Fu X, Ivanov S, Zhang P, Sheng L, Wu D, et al. DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA. EMBO J. 2005;24:779-89 pubmed
    ..Thus, our findings establish a novel role for DNA-PKcs in CpG-DNA signaling and define a CpG-DNA/DNA-PKcs/Akt pathway. ..
  26. Sand Dejmek J, Adelmant G, Sobhian B, Calkins A, Marto J, Iglehart D, et al. Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT) in DNA repair, apoptosis and necrosis after cisplatin. Mol Cancer. 2011;10:74 pubmed publisher
    ..Silencing FACT however, allows both apoptosis and necrosis. Targeting DNA repair in cancer patients may have different therapeutic effects depending upon the roles played by factors targeted. ..
  27. Lou Z, Chen B, Asaithamby A, Minter Dykhouse K, Chen D, Chen J. MDC1 regulates DNA-PK autophosphorylation in response to DNA damage. J Biol Chem. 2004;279:46359-62 pubmed
    ..Therefore, MDC1 acts not only as a mediator of DNA damage checkpoint but also as a mediator of DNA damage repair. ..
  28. Chan D, Chen B, Prithivirajsingh S, Kurimasa A, Story M, Qin J, et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev. 2002;16:2333-8 pubmed
    ..Mutation of Thr2609 to Ala leads to radiation sensitivity and impaired DSB rejoining. These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ. ..
  29. Fang L, Wang Y, Du D, Yang G, Tak Kwok T, Kai Kong S, et al. Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Res. 2007;17:100-16 pubmed
    ..These findings identify Par3 as a novel component of the DNA-PK complex and implicate an unexpected link of cell polarity to DSB repair. ..
  30. Spagnolo L, Rivera Calzada A, Pearl L, Llorca O. Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair. Mol Cell. 2006;22:511-9 pubmed
  31. An J, Yang D, Xu Q, Zhang S, Huo Y, Shang Z, et al. DNA-dependent protein kinase catalytic subunit modulates the stability of c-Myc oncoprotein. Mol Cancer. 2008;7:32 pubmed publisher
    ..Our results suggest DNA-PKcs a novel biological role beyond its DNA repair function. ..
  32. Pankotai T, Bonhomme C, Chen D, Soutoglou E. DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks. Nat Struct Mol Biol. 2012;19:276-82 pubmed publisher
    ..Upon inhibition of DNA protein kinase (DNAPK), RNAPII bypasses the break and continues transcription elongation, suggesting that it is not the break per se ..
  33. Song Q, Burrows S, Smith G, Lees Miller S, Kumar S, Chan D, et al. Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing. J Exp Med. 1996;184:619-26 pubmed
    ..This study demonstrates for the first time that the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE-like protease. ..
  34. Huang J, Nueda A, Yoo S, Dynan W. Heat shock transcription factor 1 binds selectively in vitro to Ku protein and the catalytic subunit of the DNA-dependent protein kinase. J Biol Chem. 1997;272:26009-16 pubmed
    ..The ability of HSF1 to interact with both components of DNA-PK provides a potential mechanism for the activation of DNA-PK in response to heat and other forms of stress. ..
  35. Calsou P, Delteil C, Frit P, Drouet J, Salles B. Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. J Mol Biol. 2003;326:93-103 pubmed
    ..DNA-PK comprises Ku70/Ku80 heterodimer and the kinase subunit DNA-PKcs (p460)...
  36. Ma Y, Lu H, Tippin B, Goodman M, Shimazaki N, Koiwai O, et al. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol Cell. 2004;16:701-13 pubmed
    ..The XRCC4:DNA ligase IV complex is able to ligate one strand that has only minimal base pairing with the antiparallel strand. This important aspect of the ligation leads to an iterative strand-processing model for the steps of NHEJ. ..
  37. Someya M, Sakata K, Matsumoto Y, Yamamoto H, Monobe M, Ikeda H, et al. The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer. Carcinogenesis. 2006;27:117-22 pubmed
    ..DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer. ..
  38. Lu D, Huang J, Basu A. Protein kinase Cepsilon activates protein kinase B/Akt via DNA-PK to protect against tumor necrosis factor-alpha-induced cell death. J Biol Chem. 2006;281:22799-807 pubmed
    ..These results suggest that PKCepsilon activates Akt via DNA-PK to mediate its antiapoptotic function. Furthermore, we report for the first time that DNA-PK can regulate receptor-initiated apoptosis via Akt. ..
  39. Li L, Olvera J, Yoder K, Mitchell R, Butler S, Lieber M, et al. Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. EMBO J. 2001;20:3272-81 pubmed
    ..We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal. ..
  40. Burma S, Chen D. Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst). 2004;3:909-18 pubmed
    ..The many roles of DNA-PK in the mammalian cell are discussed in this review with particular emphasis on recent advances in our understanding of the phosphorylation events that take place during the activation of DNA-PK at DNA breaks. ..
  41. Li Y, Zhao Y, Jiang R, Xu Y, Ling M, Pang Y, et al. DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis in human embryo lung fibroblast cells. Toxicol Lett. 2012;210:302-10 pubmed publisher
    ..These results suggest that DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis. ..
  42. Shao R, Cao C, Zhang H, Kohn K, Wold M, Pommier Y. Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. EMBO J. 1999;18:1397-406 pubmed
    ..camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation ..
  43. Chan D, Son S, Block W, Ye R, Khanna K, Wold M, et al. Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase. J Biol Chem. 2000;275:7803-10 pubmed
    ..The related protein, DNA-dependent protein kinase catalytic subunit, also phosphorylated PHAS-I, RPA, and Chk2 in the presence of manganese, suggesting that the requirement for manganese is a characteristic of this class of enzyme. ..
  44. Lucero H, Gae D, Taccioli G. Novel localization of the DNA-PK complex in lipid rafts: a putative role in the signal transduction pathway of the ionizing radiation response. J Biol Chem. 2003;278:22136-43 pubmed
    ..Thus, we speculate that another role for the DNA-PKcs subunit and perhaps for the holoenzyme is in the signal transduction of IR response. ..
  45. Park E, Chan D, Park J, Oettinger M, Kwon J. DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic Acids Res. 2003;31:6819-27 pubmed
  46. Javvadi P, Makino H, Das A, Lin Y, Chen D, Chen B, et al. Threonine 2609 phosphorylation of the DNA-dependent protein kinase is a critical prerequisite for epidermal growth factor receptor-mediated radiation resistance. Mol Cancer Res. 2012;10:1359-68 pubmed publisher
    ..Our study underscores the critical importance of a reciprocal relationship between DNA-PKcs phosphorylation and EGFR-mediated radiation response and elucidates mechanisms underlying mutant EGFR-associated radiosensitivity in NSCLCs. ..
  47. Davis A, Chen B, Chen D. DNA-PK: a dynamic enzyme in a versatile DSB repair pathway. DNA Repair (Amst). 2014;17:21-9 pubmed publisher
    ..In this review we will describe the important factors and mechanisms modulating NHEJ with emphasis given to the versatility of this repair process and the DNA-PK complex. ..
  48. Suzuki K, Kodama S, Watanabe M. Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation. J Biol Chem. 1999;274:25571-5 pubmed
    ..These results indicate that the ATM protein is recruited to the site of DNA damage and it recognizes double strand breaks by itself or through an association with other DNA-binding protein other than DNA-PK and Ku80 proteins. ..
  49. Wang H, Wang M, Wang H, Böcker W, Iliakis G. Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors. J Cell Physiol. 2005;202:492-502 pubmed
    ..The results in aggregate implicate DNA-PK, ATM and possibly other kinases in H2AX phosphorylation. The functional significance and the mechanisms of coordination in space and time of these multiple inputs require further investigation. ..
  50. Drouet J, Delteil C, Lefrançois J, Concannon P, Salles B, Calsou P. DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks. J Biol Chem. 2005;280:7060-9 pubmed
    ..Altogether these results offer insights into the interplay between key NHEJ proteins during this repair process in the cell. ..
  51. Reitsema T, Klokov D, Banath J, Olive P. DNA-PK is responsible for enhanced phosphorylation of histone H2AX under hypertonic conditions. DNA Repair (Amst). 2005;4:1172-81 pubmed
    ..We suggest that hypertonic treatment following irradiation inhibits double-strand break rejoining that in turn maintains DNA-PK activity at the site of the break, enhancing the size of the gammaH2AX foci. ..
  52. Mi J, Dziegielewski J, Bolesta E, Brautigan D, Larner J. Activation of DNA-PK by ionizing radiation is mediated by protein phosphatase 6. PLoS ONE. 2009;4:e4395 pubmed publisher
    ..Our data demonstrate that PP6 associates with and activates DNA-PK in response to ionizing radiation. Therefore, the PP6/PP6R1 phosphatase is a potential molecular target for radiation sensitization by chemical inhibition. ..
  53. Gangwar R, Ahirwar D, Mandhani A, Mittal R. Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population?. Mutat Res. 2009;680:56-63 pubmed publisher
    ..and 250 controls to investigate the association between OGG1 (C1245G rs1052133), XRCC3 (C18067T, rs861539) and XRCC7 (G6721T, rs7003908) polymorphisms and bladder cancer susceptibility by PCR-RFLP and the ARMS method...
  54. Singleton B, Torres Arzayus M, Rottinghaus S, Taccioli G, Jeggo P. The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit. Mol Cell Biol. 1999;19:3267-77 pubmed
    ..This residue is conserved among species and lies outside of the previously reported Ku70-Ku80 interaction domain. The mutational change nonetheless abrogates the Ku70-Ku80 interaction and DNA end-binding activity. ..
  55. Park S, Oh E, Yoo M, Lee S. Involvement of DNA-dependent protein kinase in regulation of stress-induced JNK activation. DNA Cell Biol. 2001;20:637-45 pubmed
    ..Together, our results suggest that DNA damage induces physical interaction between DNA-PK and JNK, which may in turn negatively affect JNK activity through JNK phosphorylation by DNA-PK. ..
  56. Dittmann K, Mayer C, Fehrenbacher B, Schaller M, Raju U, Milas L, et al. Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem. 2005;280:31182-9 pubmed
    ..Our data implicate a novel function of the EGFR during DNA repair processes. ..
  57. Hartley K, Gell D, Smith G, Zhang H, Divecha N, Connelly M, et al. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell. 1995;82:849-56 pubmed
    ..The relationship of these proteins to DNA-PKcs provides important clues to their mechanisms of action. ..
  58. Feng J, Park J, Cron P, Hess D, Hemmings B. Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase. J Biol Chem. 2004;279:41189-96 pubmed
    ..We conclude that DNA-PK is a long sought after kinase responsible for the Ser-473 phosphorylation step in the activation of PKB...
  59. Heo K, Kim H, Choi S, Choi J, Kim K, Gu J, et al. FACT-mediated exchange of histone variant H2AX regulated by phosphorylation of H2AX and ADP-ribosylation of Spt16. Mol Cell. 2008;30:86-97 pubmed publisher
    ..Thus, these data establish FACT as the major regulator involved in H2AX exchange process that is modulated by H2AX phosphorylation and Spt16 ADP-ribosylation. ..
  60. Malewicz M, Kadkhodaei B, Kee N, Volakakis N, Hellman U, Viktorsson K, et al. Essential role for DNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors in DNA double-strand break repair. Genes Dev. 2011;25:2031-40 pubmed publisher
    ..Thus, NR4As represent an entirely novel component of DNA damage response and are substrates of DNA-PK in the process of DSB repair. ..
  61. Jin S, Kharbanda S, Mayer B, Kufe D, Weaver D. Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit. J Biol Chem. 1997;272:24763-6 pubmed
    ..c-Abl phosphorylation of DNA-PKcs disassociates the DNA-PKcs.Ku complex. Thus, Ku and c-Abl provide opposing functions with regard to DNA-PK activity. ..
  62. Kysela B, Chovanec M, Jeggo P. Phosphorylation of linker histones by DNA-dependent protein kinase is required for DNA ligase IV-dependent ligation in the presence of histone H1. Proc Natl Acad Sci U S A. 2005;102:1877-82 pubmed
    ..Thus, by using histone H1-bound DNA as a template, we have reconstituted the end-joining step of DNA nonhomologous end-joining in vitro with a requirement for DNA-PK. ..
  63. Ariumi Y, Masutani M, Copeland T, Mimori T, Sugimura T, Shimotohno K, et al. Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro. Oncogene. 1999;18:4616-25 pubmed
    ..Thus, DNA-PK suppresses PARP activity, probably through direct binding and/or sequestration of DNA-ends which serve as an important stimulator for both enzymes. ..
  64. Poinsignon C, Moshous D, Callebaut I, de Chasseval R, Villey I, de Villartay J. The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination. J Exp Med. 2004;199:315-21 pubmed
  65. Mayeur G, Kung W, Martinez A, Izumiya C, Chen D, Kung H. Ku is a novel transcriptional recycling coactivator of the androgen receptor in prostate cancer cells. J Biol Chem. 2005;280:10827-33 pubmed
    ..Finally, in vitro transcription assays demonstrated Ku involvement in transcriptional recycling with androgen dependent promoters. ..
  66. Takai H, Wang R, Takai K, Yang H, de Lange T. Tel2 regulates the stability of PI3K-related protein kinases. Cell. 2007;131:1248-59 pubmed
    ..These data identify Tel2 as a highly conserved regulator of PIKK stability. ..
  67. Shimomura A, Takasaki A, Nomura R, Hayashi N, Senda T. Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1. Med Mol Morphol. 2013;46:14-9 pubmed publisher
    ..Identification of the interaction between LEF1 and DNA-PKcs may provide clues for a novel therapy for cancer treatment as well as for understanding LEF1-mediated transcriptional regulation. ..
  68. Huang B, Shang Z, Li B, Wang Y, Liu X, Zhang S, et al. DNA-PKcs associates with PLK1 and is involved in proper chromosome segregation and cytokinesis. J Cell Biochem. 2014;115:1077-88 pubmed publisher
    ..Our results demonstrate the functional association of DNA-PKcs with PLK1, especially in chromosomal segregation and cytokinesis control. ..
  69. Zernik Kobak M, Vasunia K, Connelly M, Anderson C, Dixon K. Sites of UV-induced phosphorylation of the p34 subunit of replication protein A from HeLa cells. J Biol Chem. 1997;272:23896-904 pubmed
    ..The capacity of purified DNA-PK to phosphorylate many of these same sites on RPA-p34 in vitro implicates DNA-PK or a kinase with similar specificity in the UV-induced hyperphosphorylation of RPA in vivo. ..
  70. Convery E, Shin E, Ding Q, Wang W, Douglas P, Davis L, et al. Inhibition of homologous recombination by variants of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). Proc Natl Acad Sci U S A. 2005;102:1345-50 pubmed
  71. Shahi A, Lee J, Kang Y, Lee S, Hyun J, Chang I, et al. Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair. Nucleic Acids Res. 2011;39:2130-43 pubmed publisher
    ..These results suggest a potential role for MSH6 in DSB repair through upregulation of NHEJ by association with Ku70. ..
  72. Neal J, Dang V, Douglas P, Wold M, Lees Miller S, Meek K. Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation. Mol Cell Biol. 2011;31:1719-33 pubmed publisher
  73. Liaw H, Lee D, Myung K. DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange. PLoS ONE. 2011;6:e21424 pubmed publisher
    ..This pathway thus permits cells to repair DNA damage properly and increase cell viability. ..
  74. Baekelandt V, Claeys A, Cherepanov P, De Clercq E, De Strooper B, Nuttin B, et al. DNA-Dependent protein kinase is not required for efficient lentivirus integration. J Virol. 2000;74:11278-85 pubmed
    ..However, no inhibition of lentivirus vector-mediated transduction or HIV-1 replication by 3-methoxybenzamide, a known PARP inhibitor, was observed. In conclusion, DNA-PK and PARP are not essential for lentivirus integration. ..
  75. Veuger S, Curtin N, Smith G, Durkacz B. Effects of novel inhibitors of poly(ADP-ribose) polymerase-1 and the DNA-dependent protein kinase on enzyme activities and DNA repair. Oncogene. 2004;23:7322-9 pubmed
    ..These data point to combined inhibition of PARP-1 and DNA-PK as a powerful strategy for tumor radiosensitization. ..
  76. Wang L, Bondy M, Shen H, El Zein R, Aldape K, Cao Y, et al. Polymorphisms of DNA repair genes and risk of glioma. Cancer Res. 2004;64:5560-3 pubmed
    ..breaks, such as XRCC1 in single-strand break repair, XRCC3 and RAD51 in homologous recombination repair, and XRCC7 in nonhomologous end joining double-strand break repair...
  77. Hirata H, Hinoda Y, Matsuyama H, Tanaka Y, Okayama N, Suehiro Y, et al. Polymorphisms of DNA repair genes are associated with renal cell carcinoma. Biochem Biophys Res Commun. 2006;342:1058-62 pubmed
    ..the genotypic frequency of six different polymorphic loci on five DNA repair genes (XRCC1, XPC, ERCC1, XRCC3, and XRCC7). The chi(2) test was applied to compare the genotype frequency between patients and controls...
  78. Ju B, Lunyak V, Perissi V, Garcia Bassets I, Rose D, Glass C, et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science. 2006;312:1798-802 pubmed
    ..Our data mechanistically link DNA topoisomerase IIbeta-dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription. ..
  79. Ruis B, Fattah K, Hendrickson E. The catalytic subunit of DNA-dependent protein kinase regulates proliferation, telomere length, and genomic stability in human somatic cells. Mol Cell Biol. 2008;28:6182-95 pubmed publisher
    ..Surprisingly, DNA-PK(cs) does not appear to be essential, although the cell line lacking this gene has profound proliferation and genomic stability deficits not observed for other mammalian systems. ..
  80. van der Burg M, Ijspeert H, Verkaik N, Turul T, Wiegant W, Morotomi Yano K, et al. A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. J Clin Invest. 2009;119:91-8 pubmed publisher
    ..Further, the data suggest that residual DNA-PKcs activity is indispensable in humans. ..
  81. Sibanda B, Chirgadze D, Blundell T. Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Nature. 2010;463:118-21 pubmed publisher
    ..The carboxy-terminal kinase domain is located on top of this structure, and a small HEAT repeat domain that probably binds DNA is inside. The structure provides a flexible cradle to promote DNA double-strand-break repair. ..
  82. Sipley J, Menninger J, Hartley K, Ward D, Jackson S, Anderson C. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci U S A. 1995;92:7515-9 pubmed
    ..This location is coincident with that of XRCC7, the gene that complements the DNA double-strand break repair and V(D)J recombination defects (where V is variable,..
  83. Song S, Lu Y, Choi Y, Han Y, Tang Q, Zhao G, et al. DNA-dependent PK inhibits adeno-associated virus DNA integration. Proc Natl Acad Sci U S A. 2004;101:2112-6 pubmed
    ..In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo. ..
  84. Taylor T, Knipe D. Proteomics of herpes simplex virus replication compartments: association of cellular DNA replication, repair, recombination, and chromatin remodeling proteins with ICP8. J Virol. 2004;78:5856-66 pubmed
    ..We hypothesize that some of the proteins coprecipitating with ICP8 are involved in HSV replication and may give new insight into viral replication mechanisms. ..
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    ..The functional association between XRCC1 and DNA-PK in response to IR provides the first evidence for their involvement in a common DSB repair pathway. ..
  86. Shao S, Cai Y, Wang Q, Yan L, Zhao X, Wang L. [Expression of GLUT-1, p63 and DNA-Pkcs in serous ovarian tumors and their significance]. Zhonghua Zhong Liu Za Zhi. 2007;29:697-700 pubmed
    ..05). The results suggest that the abnormal expression of GTUT1, p63 and DNA-Pkcs may perhaps participate in serous ovarian tumor occurrence and development and may be considered as a marker reflecting tumor malignant behavior. ..
  87. Toulany M, Kehlbach R, Florczak U, Sak A, Wang S, Chen J, et al. Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Ther. 2008;7:1772-81 pubmed publisher
    ..Thus, targeting of AKT enhances radiation sensitivity of lung cancer cell lines A549 and H460 most likely through specific inhibition of DNA-PKcs-dependent DNA-dsb repair but not through enhancement of radiation-induced apoptosis. ..
  88. Karmakar P, Piotrowski J, Brosh R, Sommers J, Miller S, Cheng W, et al. Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation. J Biol Chem. 2002;277:18291-302 pubmed
    ..Thus, WRN protein is a target for DNA-PK phosphorylation in vitro and in vivo, and this phosphorylation may be a way of regulating its different catalytic activities, possibly in the repair of DNA dsb. ..
  89. Shintani S, Mihara M, Li C, Nakahara Y, Hino S, Nakashiro K, et al. Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma. Cancer Sci. 2003;94:894-900 pubmed
    ..DNA-PKcs might be a molecular target for a novel radiation sensitization therapy of OSCC. ..
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    ..These results indicate that CK2 has an important role in the modulation of DNA-PKcs activity and its phosphorylation status providing important insights into the mechanisms by which DNA-PKcs is regulated in vivo. ..
  91. Iijima S, Teraoka H, Date T, Tsukada K. DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein. Eur J Biochem. 1992;206:595-603 pubmed
    ..Phosphopeptide mapping and phosphoamino acid analysis indicated that DNA-PK phosphorylates c-Myc in vitro at several serine residues. ..
  92. Daniel R, Katz R, Merkel G, Hittle J, Yen T, Skalka A. Wortmannin potentiates integrase-mediated killing of lymphocytes and reduces the efficiency of stable transduction by retroviruses. Mol Cell Biol. 2001;21:1164-72 pubmed
    ..The studies also suggest that cells can be sensitized to such killing and stable retroviral DNA integration blocked by drugs that inhibit cellular DNA repair pathways. ..