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Nucleic Acids Res. Apr 1, 1998; 26(7): 1551–1559.
PMCID: PMC147477

Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids.

Abstract

The Ku protein-DNA-dependent protein kinase system is one of the major pathways by which cells of higher eukaryotes respond to double-strand DNA breaks. The components of the system are evolutionarily conserved and homologs are known from a number of organisms. The Ku protein component binds directly to DNA ends and may help align them for ligation. Binding of Ku protein to DNA also nucleates formation of an active enzyme complex containing the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The interaction between Ku protein, DNA-PKcs and nucleic acids has been extensively investigated. This review summarizes the results of these biochemical investigations and relates them to recent molecular genetic studies that reveal highly characteristic repair and recombination defects in mutant cells lacking Ku protein or DNA-PKcs.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Mimori T, Akizuki M, Yamagata H, Inada S, Yoshida S, Homma M. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest. 1981 Sep;68(3):611–620. [PMC free article] [PubMed]
  • Mimori T, Hardin JA, Steitz JA. Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. J Biol Chem. 1986 Feb 15;261(5):2274–2278. [PubMed]
  • Francoeur AM, Peebles CL, Gompper PT, Tan EM. Identification of Ki (Ku, p70/p80) autoantigens and analysis of anti-Ki autoantibody reactivity. J Immunol. 1986 Mar 1;136(5):1648–1653. [PubMed]
  • Reeves WH. Use of monoclonal antibodies for the characterization of novel DNA-binding proteins recognized by human autoimmune sera. J Exp Med. 1985 Jan 1;161(1):18–39. [PMC free article] [PubMed]
  • Reeves WH. Antibodies to the p70/p80 (Ku) antigens in systemic lupus erythematosus. Rheum Dis Clin North Am. 1992 May;18(2):391–414. [PubMed]
  • Yaneva M, Arnett FC. Antibodies against Ku protein in sera from patients with autoimmune diseases. Clin Exp Immunol. 1989 Jun;76(3):366–372. [PMC free article] [PubMed]
  • Olhoffer IH, Peng SL, Craft J. Revisiting autoantibody profiles in systemic lupus erythematosus. J Rheumatol. 1997 Feb;24(2):297–302. [PubMed]
  • Mimori T, Hardin JA. Mechanism of interaction between Ku protein and DNA. J Biol Chem. 1986 Aug 5;261(22):10375–10379. [PubMed]
  • Walker AI, Hunt T, Jackson RJ, Anderson CW. Double-stranded DNA induces the phosphorylation of several proteins including the 90 000 mol. wt. heat-shock protein in animal cell extracts. EMBO J. 1985 Jan;4(1):139–145. [PMC free article] [PubMed]
  • Lees-Miller SP, Chen YR, Anderson CW. Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen. Mol Cell Biol. 1990 Dec;10(12):6472–6481. [PMC free article] [PubMed]
  • Carter T, Vancurová I, Sun I, Lou W, DeLeon S. A DNA-activated protein kinase from HeLa cell nuclei. Mol Cell Biol. 1990 Dec;10(12):6460–6471. [PMC free article] [PubMed]
  • Dvir A, Peterson SR, Knuth MW, Lu H, Dynan WS. Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11920–11924. [PMC free article] [PubMed]
  • Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993 Jan 15;72(1):131–142. [PubMed]
  • Taccioli GE, Gottlieb TM, Blunt T, Priestley A, Demengeot J, Mizuta R, Lehmann AR, Alt FW, Jackson SP, Jeggo PA. Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science. 1994 Sep 2;265(5177):1442–1445. [PubMed]
  • Rathmell WK, Chu G. Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7623–7627. [PMC free article] [PubMed]
  • Smider V, Rathmell WK, Lieber MR, Chu G. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science. 1994 Oct 14;266(5183):288–291. [PubMed]
  • Getts RC, Stamato TD. Absence of a Ku-like DNA end binding activity in the xrs double-strand DNA repair-deficient mutant. J Biol Chem. 1994 Jun 10;269(23):15981–15984. [PubMed]
  • Porter SE, Greenwell PW, Ritchie KB, Petes TD. The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 1996 Feb 15;24(4):582–585. [PMC free article] [PubMed]
  • Boulton SJ, Jackson SP. Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 1996 Dec 1;24(23):4639–4648. [PMC free article] [PubMed]
  • Yang SH, Nussenzweig A, Li L, Kim D, Ouyang H, Burgman P, Li GC. Modulation of thermal induction of hsp70 expression by Ku autoantigen or its individual subunits. Mol Cell Biol. 1996 Jul;16(7):3799–3806. [PMC free article] [PubMed]
  • Li GC, Yang SH, Kim D, Nussenzweig A, Ouyang H, Wei J, Burgman P, Li L. Suppression of heat-induced hsp70 expression by the 70-kDa subunit of the human Ku autoantigen. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4512–4516. [PMC free article] [PubMed]
  • Peterson SR, Jesch SA, Chamberlin TN, Dvir A, Rabindran SK, Wu C, Dynan WS. Stimulation of the DNA-dependent protein kinase by RNA polymerase II transcriptional activator proteins. J Biol Chem. 1995 Jan 20;270(3):1449–1454. [PubMed]
  • Huang J, Nueda A, Yoo S, Dynan WS. 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 Oct 10;272(41):26009–26016. [PubMed]
  • Chan JY, Lerman MI, Prabhakar BS, Isozaki O, Santisteban P, Kuppers RC, Oates EL, Notkins AL, Kohn LD. Cloning and characterization of a cDNA that encodes a 70-kDa novel human thyroid autoantigen. J Biol Chem. 1989 Mar 5;264(7):3651–3654. [PubMed]
  • Reeves WH, Sthoeger ZM. Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J Biol Chem. 1989 Mar 25;264(9):5047–5052. [PubMed]
  • Yaneva M, Wen J, Ayala A, Cook R. cDNA-derived amino acid sequence of the 86-kDa subunit of the Ku antigen. J Biol Chem. 1989 Aug 15;264(23):13407–13411. [PubMed]
  • Mimori T, Ohosone Y, Hama N, Suwa A, Akizuki M, Homma M, Griffith AJ, Hardin JA. Isolation and characterization of cDNA encoding the 80-kDa subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1777–1781. [PMC free article] [PubMed]
  • Porges AJ, Ng T, Reeves WH. Antigenic determinants of the Ku (p70/p80) autoantigen are poorly conserved between species. J Immunol. 1990 Dec 15;145(12):4222–4228. [PubMed]
  • Falzon M, Kuff EL. The nucleotide sequence of a mouse cDNA encoding the 80 kDa subunit of the Ku (p70/p80) autoantigen. Nucleic Acids Res. 1992 Jul 25;20(14):3784–3784. [PMC free article] [PubMed]
  • Griffith AJ, Craft J, Evans J, Mimori T, Hardin JA. Nucleotide sequence and genomic structure analyses of the p70 subunit of the human Ku autoantigen: evidence for a family of genes encoding Ku (p70)-related polypeptides. Mol Biol Rep. 1992 May;16(2):91–97. [PubMed]
  • Feldmann H, Winnacker EL. A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae. J Biol Chem. 1993 Jun 15;268(17):12895–12900. [PubMed]
  • Jacoby DB, Wensink PC. Yolk protein factor 1 is a Drosophila homolog of Ku, the DNA-binding subunit of a DNA-dependent protein kinase from humans. J Biol Chem. 1994 Apr 15;269(15):11484–11491. [PubMed]
  • Beall EL, Admon A, Rio DC. A Drosophila protein homologous to the human p70 Ku autoimmune antigen interacts with the P transposable element inverted repeats. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12681–12685. [PMC free article] [PubMed]
  • Milne GT, Jin S, Shannon KB, Weaver DT. Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Aug;16(8):4189–4198. [PMC free article] [PubMed]
  • Feldmann H, Driller L, Meier B, Mages G, Kellermann J, Winnacker EL. HDF2, the second subunit of the Ku homologue from Saccharomyces cerevisiae. J Biol Chem. 1996 Nov 1;271(44):27765–27769. [PubMed]
  • Lee SE, He DM, Hendrickson EA. Characterization of Chinese hamster cell lines that are x-ray-sensitive, impaired in DNA double-strand break repair and defective for V(D)J recombination. Curr Top Microbiol Immunol. 1996;217:133–142. [PubMed]
  • He DM, Lee SE, Hendrickson EA. Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D) J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA. Mutat Res. 1996 May 15;363(1):43–56. [PubMed]
  • Errami A, Smider V, Rathmell WK, He DM, Hendrickson EA, Zdzienicka MZ, Chu G. Ku86 defines the genetic defect and restores X-ray resistance and V(D)J recombination to complementation group 5 hamster cell mutants. Mol Cell Biol. 1996 Apr;16(4):1519–1526. [PMC free article] [PubMed]
  • Paesen GC, Zanotto PM, Nuttall PA. A tick homologue of the human DNA helicase II 70-kDa subunit. Biochim Biophys Acta. 1996 Mar 1;1305(3):120–124. [PubMed]
  • Barnes G, Rio D. DNA double-strand-break sensitivity, DNA replication, and cell cycle arrest phenotypes of Ku-deficient Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):867–872. [PMC free article] [PubMed]
  • Cai QQ, Plet A, Imbert J, Lafage-Pochitaloff M, Cerdan C, Blanchard JM. Chromosomal location and expression of the genes coding for Ku p70 and p80 in human cell lines and normal tissues. Cytogenet Cell Genet. 1994;65(4):221–227. [PubMed]
  • Blunt T, Taccioli GE, Priestley A, Hafezparast M, McMillan T, Liu J, Cole CC, White J, Alt FW, Jackson SP, et al. A YAC contig encompassing the XRCC5 (Ku80) DNA repair gene and complementation of defective cells by YAC protoplast fusion. Genomics. 1995 Nov 20;30(2):320–328. [PubMed]
  • May G, Sutton C, Gould H. Purification and characterization of Ku-2, an octamer-binding protein related to the autoantigen Ku. J Biol Chem. 1991 Feb 15;266(5):3052–3059. [PubMed]
  • Oderwald H, Hughes MJ, Jost JP. Non-histone protein 1 (NHP1) is a member of the Ku protein family which is upregulated in differentiating mouse myoblasts and human promyelocytes. FEBS Lett. 1996 Mar 18;382(3):313–318. [PubMed]
  • Ouyang H, Nussenzweig A, Kurimasa A, Soares VC, Li X, Cordon-Cardo C, Li W h, Cheong N, Nussenzweig M, Iliakis G, et al. Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo. J Exp Med. 1997 Sep 15;186(6):921–929. [PMC free article] [PubMed]
  • Myung K, He DM, Lee SE, Hendrickson EA. KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. EMBO J. 1997 Jun 2;16(11):3172–3184. [PMC free article] [PubMed]
  • Wu X, Lieber MR. Protein-protein and protein-DNA interaction regions within the DNA end-binding protein Ku70-Ku86. Mol Cell Biol. 1996 Sep;16(9):5186–5193. [PMC free article] [PubMed]
  • Osipovich O, Durum SK, Muegge K. Defining the minimal domain of Ku80 for interaction with Ku70. J Biol Chem. 1997 Oct 24;272(43):27259–27265. [PubMed]
  • Paillard S, Strauss F. Analysis of the mechanism of interaction of simian Ku protein with DNA. Nucleic Acids Res. 1991 Oct 25;19(20):5619–5624. [PMC free article] [PubMed]
  • Falzon M, Fewell JW, Kuff EL. EBP-80, a transcription factor closely resembling the human autoantigen Ku, recognizes single- to double-strand transitions in DNA. J Biol Chem. 1993 May 15;268(14):10546–10552. [PubMed]
  • Pang D, Yoo S, Dynan WS, Jung M, Dritschilo A. Ku proteins join DNA fragments as shown by atomic force microscopy. Cancer Res. 1997 Apr 15;57(8):1412–1415. [PubMed]
  • Blier PR, Griffith AJ, Craft J, Hardin JA. Binding of Ku protein to DNA. Measurement of affinity for ends and demonstration of binding to nicks. J Biol Chem. 1993 Apr 5;268(10):7594–7601. [PubMed]
  • Yaneva M, Kowalewski T, Lieber MR. Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy studies. EMBO J. 1997 Aug 15;16(16):5098–5112. [PMC free article] [PubMed]
  • de Vries E, van Driel W, Bergsma WG, Arnberg AC, van der Vliet PC. HeLa nuclear protein recognizing DNA termini and translocating on DNA forming a regular DNA-multimeric protein complex. J Mol Biol. 1989 Jul 5;208(1):65–78. [PubMed]
  • Zhang WW, Yaneva M. On the mechanisms of Ku protein binding to DNA. Biochem Biophys Res Commun. 1992 Jul 15;186(1):574–579. [PubMed]
  • Knuth MW, Gunderson SI, Thompson NE, Strasheim LA, Burgess RR. Purification and characterization of proximal sequence element-binding protein 1, a transcription activating protein related to Ku and TREF that binds the proximal sequence element of the human U1 promoter. J Biol Chem. 1990 Oct 15;265(29):17911–17920. [PubMed]
  • Cary RB, Peterson SR, Wang J, Bear DG, Bradbury EM, Chen DJ. DNA looping by Ku and the DNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4267–4272. [PMC free article] [PubMed]
  • Griffith AJ, Blier PR, Mimori T, Hardin JA. Ku polypeptides synthesized in vitro assemble into complexes which recognize ends of double-stranded DNA. J Biol Chem. 1992 Jan 5;267(1):331–338. [PubMed]
  • Ono M, Tucker PW, Capra JD. Production and characterization of recombinant human Ku antigen. Nucleic Acids Res. 1994 Sep 25;22(19):3918–3924. [PMC free article] [PubMed]
  • Ochem AE, Skopac D, Costa M, Rabilloud T, Vuillard L, Simoncsits A, Giacca M, Falaschi A. Functional properties of the separate subunits of human DNA helicase II/Ku autoantigen. J Biol Chem. 1997 Nov 21;272(47):29919–29926. [PubMed]
  • Chou CH, Wang J, Knuth MW, Reeves WH. Role of a major autoepitope in forming the DNA binding site of the p70 (Ku) antigen. J Exp Med. 1992 Jun 1;175(6):1677–1684. [PMC free article] [PubMed]
  • Wang J, Satoh M, Pierani A, Schmitt J, Chou CH, Stunnenberg HG, Roeder RG, Reeves WH. Assembly and DNA binding of recombinant Ku (p70/p80) autoantigen defined by a novel monoclonal antibody specific for p70/p80 heterodimers. J Cell Sci. 1994 Nov;107(Pt 11):3223–3233. [PubMed]
  • Wang J, Satoh M, Chou CH, Reeves WH. Similar DNA binding properties of free P70 (KU) subunit and P70/P80 heterodimer. FEBS Lett. 1994 Sep 5;351(2):219–224. [PubMed]
  • Paillard S, Strauss F. Site-specific proteolytic cleavage of Ku protein bound to DNA. Proteins. 1993 Mar;15(3):330–337. [PubMed]
  • Roca J, Wang JC. The capture of a DNA double helix by an ATP-dependent protein clamp: a key step in DNA transport by type II DNA topoisomerases. Cell. 1992 Nov 27;71(5):833–840. [PubMed]
  • Kong XP, Onrust R, O'Donnell M, Kuriyan J. Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp. Cell. 1992 May 1;69(3):425–437. [PubMed]
  • Bliss TM, Lane DP. Ku selectively transfers between DNA molecules with homologous ends. J Biol Chem. 1997 Feb 28;272(9):5765–5773. [PubMed]
  • Ramsden DA, Gellert M. Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks. EMBO J. 1998 Jan 15;17(2):609–614. [PMC free article] [PubMed]
  • Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simoncsits A, Susic S, Rahman K, Marusic L, Chen J, et al. Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. EMBO J. 1994 Oct 17;13(20):4991–5001. [PMC free article] [PubMed]
  • Cao QP, Pitt S, Leszyk J, Baril EF. DNA-dependent ATPase from HeLa cells is related to human Ku autoantigen. Biochemistry. 1994 Jul 19;33(28):8548–8557. [PubMed]
  • Tuteja N, Phan TN, Tuteja R, Ochem A, Falaschi A. Inhibition of DNA unwinding and ATPase activities of human DNA helicase II by chemotherapeutic agents. Biochem Biophys Res Commun. 1997 Jul 30;236(3):636–640. [PubMed]
  • Chu G. Double strand break repair. J Biol Chem. 1997 Sep 26;272(39):24097–24100. [PubMed]
  • Jin S, Weaver DT. Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions. EMBO J. 1997 Nov 17;16(22):6874–6885. [PMC free article] [PubMed]
  • Singleton BK, Priestley A, Steingrimsdottir H, Gell D, Blunt T, Jackson SP, Lehmann AR, Jeggo PA. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol. 1997 Mar;17(3):1264–1273. [PMC free article] [PubMed]
  • Roberts MR, Miskimins WK, Ruddle FH. Nuclear proteins TREF1 and TREF2 bind to the transcriptional control element of the transferrin receptor gene and appear to be associated as a heterodimer. Cell Regul. 1989 Nov;1(1):151–164. [PMC free article] [PubMed]
  • Roberts MR, Han Y, Fienberg A, Hunihan L, Ruddle FH. A DNA-binding activity, TRAC, specific for the TRA element of the transferrin receptor gene copurifies with the Ku autoantigen. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6354–6358. [PMC free article] [PubMed]
  • Falzon M, Kuff EL. Isolation and characterization of a protein fraction that binds to enhancer core sequences in intracisternal A-particle long terminal repeats. J Biol Chem. 1989 Dec 25;264(36):21915–21922. [PubMed]
  • Alexandre S, Nakaki T, Vanhamme L, Lee AS. A binding site for the cyclic adenosine 3',5'-monophosphate-response element-binding protein as a regulatory element in the grp78 promoter. Mol Endocrinol. 1991 Dec;5(12):1862–1872. [PubMed]
  • Messier H, Fuller T, Mangal S, Brickner H, Igarashi S, Gaikwad J, Fotedar R, Fotedar A. p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2685–2689. [PMC free article] [PubMed]
  • Genersch E, Eckerskorn C, Lottspeich F, Herzog C, Kühn K, Pöschl E. Purification of the sequence-specific transcription factor CTCBF, involved in the control of human collagen IV genes: subunits with homology to Ku antigen. EMBO J. 1995 Feb 15;14(4):791–800. [PMC free article] [PubMed]
  • Chung U, Igarashi T, Nishishita T, Iwanari H, Iwamatsu A, Suwa A, Mimori T, Hata K, Ebisu S, Ogata E, et al. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J Biol Chem. 1996 Apr 12;271(15):8593–8598. [PubMed]
  • Giffin W, Kwast-Welfeld J, Rodda DJ, Préfontaine GG, Traykova-Andonova M, Zhang Y, Weigel NL, Lefebvre YA, Haché RJ. 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 Feb 28;272(9):5647–5658. [PubMed]
  • Okumura K, Takagi S, Sakaguchi G, Naito K, Minoura-Tada N, Kobayashi H, Mimori T, Hinuma Y, Igarashi H. Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat. FEBS Lett. 1994 Dec 12;356(1):94–100. [PubMed]
  • Okumura K, Sakaguchi G, Takagi S, Naito K, Mimori T, Igarashi H. Sp1 family proteins recognize the U5 repressive element of the long terminal repeat of human T cell leukemia virus type I through binding to the CACCC core motif. J Biol Chem. 1996 May 31;271(22):12944–12950. [PubMed]
  • Giffin W, Torrance H, Rodda DJ, Préfontaine GG, Pope L, Hache RJ. Sequence-specific DNA binding by Ku autoantigen and its effects on transcription. Nature. 1996 Mar 21;380(6571):265–268. [PubMed]
  • Quinn JP, Farina AR. Autoimmune antigen Ku is enriched on oligonucleotide columns distinct from those containing the octamer binding protein DNA consensus sequence. FEBS Lett. 1991 Jul 29;286(1-2):225–228. [PubMed]
  • Kim D, Ouyang H, Yang SH, Nussenzweig A, Burgman P, Li GC. A constitutive heat shock element-binding factor is immunologically identical to the Ku autoantigen. J Biol Chem. 1995 Jun 23;270(25):15277–15284. [PubMed]
  • Tóth EC, Marusic L, Ochem A, Patthy A, Pongor S, Giacca M, Falaschi A. Interactions of USF and Ku antigen with a human DNA region containing a replication origin. Nucleic Acids Res. 1993 Jul 11;21(14):3257–3263. [PMC free article] [PubMed]
  • DiCroce PA, Krontiris TG. The BCL2 major breakpoint region is a sequence- and cell-cycle-specific binding site of the Ku antigen. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10137–10141. [PMC free article] [PubMed]
  • Lai JS, Herr W. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958–6962. [PMC free article] [PubMed]
  • Suwa A, Hirakata M, Takeda Y, Jesch SA, Mimori T, Hardin JA. DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6904–6908. [PMC free article] [PubMed]
  • Kaczmarski W, Khan SA. Lupus autoantigen Ku protein binds HIV-1 TAR RNA in vitro. Biochem Biophys Res Commun. 1993 Oct 29;196(2):935–942. [PubMed]
  • Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990 Aug 3;249(4968):505–510. [PubMed]
  • Yoo S, Dynan WS. Characterization of the RNA binding properties of Ku protein. Biochemistry. 1998 Feb 3;37(5):1336–1343. [PubMed]
  • Sipley JD, Menninger JC, Hartley KO, Ward DC, Jackson SP, Anderson CW. 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 Aug 1;92(16):7515–7519. [PMC free article] [PubMed]
  • Hartley KO, Gell D, Smith GC, Zhang H, Divecha N, Connelly MA, Admon A, Lees-Miller SP, Anderson CW, Jackson SP. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell. 1995 Sep 8;82(5):849–856. [PubMed]
  • Araki R, Fujimori A, Hamatani K, Mita K, Saito T, Mori M, Fukumura R, Morimyo M, Muto M, Itoh M, et al. Nonsense mutation at Tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2438–2443. [PMC free article] [PubMed]
  • Shin EK, Perryman LE, Meek K. A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation. J Immunol. 1997 Apr 15;158(8):3565–3569. [PubMed]
  • Labhart P. mRNA encoding the catalytic subunit of DNA-dependent protein kinase is widely expressed in Xenopus cells. Gene. 1997 Dec 12;203(2):235–240. [PubMed]
  • Connelly MA, Zhang H, Kieleczawa J, Anderson CW. Alternate splice-site utilization in the gene for the catalytic subunit of the DNA-activated protein kinase, DNA-PKcs. Gene. 1996 Oct 10;175(1-2):271–273. [PubMed]
  • Poltoratsky VP, Shi X, York JD, Lieber MR, Carter TH. Human DNA-activated protein kinase (DNA-PK) is homologous to phosphatidylinositol kinases. J Immunol. 1995 Nov 15;155(10):4529–4533. [PubMed]
  • Lees-Miller SP, Anderson CW. The DNA-activated protein kinase, DNA-PK: a potential coordinator of nuclear events. Cancer Cells. 1991 Sep;3(9):341–346. [PubMed]
  • Finnie NJ, Gottlieb TM, Blunt T, Jeggo PA, Jackson SP. DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-strand break repair. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):320–324. [PMC free article] [PubMed]
  • Take Y, Kumano M, Hamano Y, Fukatsu H, Teraoka H, Nishimura S, Okuyama A. OK-1035, a selective inhibitor of DNA-dependent protein kinase. Biochem Biophys Res Commun. 1995 Oct 4;215(1):41–47. [PubMed]
  • Take Y, Kumano M, Teraoka H, Nishimura S, Okuyama A. DNA-dependent protein kinase inhibitor (OK-1035) suppresses p21 expression in HCT116 cells containing wild-type p53 induced by adriamycin. Biochem Biophys Res Commun. 1996 Apr 16;221(2):207–212. [PubMed]
  • Jin S, Kharbanda S, Mayer B, Kufe D, Weaver DT. Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit. J Biol Chem. 1997 Oct 3;272(40):24763–24766. [PubMed]
  • Chan DW, Lees-Miller SP. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J Biol Chem. 1996 Apr 12;271(15):8936–8941. [PubMed]
  • Casciola-Rosen LA, Anhalt GJ, Rosen A. DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis. J Exp Med. 1995 Dec 1;182(6):1625–1634. [PMC free article] [PubMed]
  • Teraoka H, Yumoto Y, Watanabe F, Tsukada K, Suwa A, Enari M, Nagata S. CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme. FEBS Lett. 1996 Sep 9;393(1):1–6. [PubMed]
  • Han Z, Malik N, Carter T, Reeves WH, Wyche JH, Hendrickson EA. DNA-dependent protein kinase is a target for a CPP32-like apoptotic protease. J Biol Chem. 1996 Oct 4;271(40):25035–25040. [PubMed]
  • Song Q, Lees-Miller SP, Kumar S, Zhang Z, Chan DW, Smith GC, Jackson SP, Alnemri ES, Litwack G, Khanna KK, et al. DNA-dependent protein kinase catalytic subunit: a target for an ICE-like protease in apoptosis. EMBO J. 1996 Jul 1;15(13):3238–3246. [PMC free article] [PubMed]
  • Casciola-Rosen L, Nicholson DW, Chong T, Rowan KR, Thornberry NA, Miller DK, Rosen A. Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. J Exp Med. 1996 May 1;183(5):1957–1964. [PMC free article] [PubMed]
  • McConnell KR, Dynan WS, Hardin JA. The DNA-dependent protein kinase catalytic subunit (p460) is cleaved during Fas-mediated apoptosis in Jurkat cells. J Immunol. 1997 Mar 1;158(5):2083–2089. [PubMed]
  • Morozov VE, Falzon M, Anderson CW, Kuff EL. DNA-dependent protein kinase is activated by nicks and larger single-stranded gaps. J Biol Chem. 1994 Jun 17;269(24):16684–16688. [PubMed]
  • Turchi JJ, Henkels K. Human Ku autoantigen binds cisplatin-damaged DNA but fails to stimulate human DNA-activated protein kinase. J Biol Chem. 1996 Jun 7;271(23):13861–13867. [PubMed]
  • Dvir A, Stein LY, Calore BL, Dynan WS. Purification and characterization of a template-associated protein kinase that phosphorylates RNA polymerase II. J Biol Chem. 1993 May 15;268(14):10440–10447. [PubMed]
  • Kharbanda S, Pandey P, Jin S, Inoue S, Bharti A, Yuan ZM, Weichselbaum R, Weaver D, Kufe D. Functional interaction between DNA-PK and c-Abl in response to DNA damage. Nature. 1997 Apr 17;386(6626):732–735. [PubMed]
  • Watanabe F, Shirakawa H, Yoshida M, Tsukada K, Teraoka H. Stimulation of DNA-dependent protein kinase activity by high mobility group proteins 1 and 2. Biochem Biophys Res Commun. 1994 Jul 29;202(2):736–742. [PubMed]
  • Boubnov NV, Hall KT, Wills Z, Lee SE, He DM, Benjamin DM, Pulaski CR, Band H, Reeves W, Hendrickson EA, et al. Complementation of the ionizing radiation sensitivity, DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):890–894. [PMC free article] [PubMed]
  • Kirchgessner CU, Patil CK, Evans JW, Cuomo CA, Fried LM, Carter T, Oettinger MA, Brown JM. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science. 1995 Feb 24;267(5201):1178–1183. [PubMed]
  • Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RS, 3rd, Barron GM, Allalunis-Turner J. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science. 1995 Feb 24;267(5201):1183–1185. [PubMed]
  • Blunt T, Finnie NJ, Taccioli GE, Smith GC, Demengeot J, Gottlieb TM, Mizuta R, Varghese AJ, Alt FW, Jeggo PA, et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell. 1995 Mar 10;80(5):813–823. [PubMed]
  • Peterson SR, Kurimasa A, Oshimura M, Dynan WS, Bradbury EM, Chen DJ. Loss of the catalytic subunit of the DNA-dependent protein kinase in DNA double-strand-break-repair mutant mammalian cells. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3171–3174. [PMC free article] [PubMed]
  • Lee SE, Mitchell RA, Cheng A, Hendrickson EA. Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle. Mol Cell Biol. 1997 Mar;17(3):1425–1433. [PMC free article] [PubMed]
  • Mages GJ, Feldmann HM, Winnacker EL. Involvement of the Saccharomyces cerevisiae HDF1 gene in DNA double-strand break repair and recombination. J Biol Chem. 1996 Apr 5;271(14):7910–7915. [PubMed]
  • Tsukamoto Y, Kato J, Ikeda H. Hdf1, a yeast Ku-protein homologue, is involved in illegitimate recombination, but not in homologous recombination. Nucleic Acids Res. 1996 Jun 1;24(11):2067–2072. [PMC free article] [PubMed]
  • Boulton SJ, Jackson SP. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO J. 1996 Sep 16;15(18):5093–5103. [PMC free article] [PubMed]
  • Siede W, Friedl AA, Dianova I, Eckardt-Schupp F, Friedberg EC. The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination. Genetics. 1996 Jan;142(1):91–102. [PMC free article] [PubMed]
  • Ramsden DA, van Gent DC, Gellert M. Specificity in V(D)J recombination: new lessons from biochemistry and genetics. Curr Opin Immunol. 1997 Feb;9(1):114–120. [PubMed]
  • Danska JS, Holland DP, Mariathasan S, Williams KM, Guidos CJ. Biochemical and genetic defects in the DNA-dependent protein kinase in murine scid lymphocytes. Mol Cell Biol. 1996 Oct;16(10):5507–5517. [PMC free article] [PubMed]
  • Blunt T, Gell D, Fox M, Taccioli GE, Lehmann AR, Jackson SP, Jeggo PA. Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10285–10290. [PMC free article] [PubMed]
  • Lieber MR, Hesse JE, Lewis S, Bosma GC, Rosenberg N, Mizuuchi K, Bosma MJ, Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 1988 Oct 7;55(1):7–16. [PubMed]
  • Nussenzweig A, Chen C, da Costa Soares V, Sanchez M, Sokol K, Nussenzweig MC, Li GC. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature. 1996 Aug 8;382(6591):551–555. [PubMed]
  • Zhu C, Bogue MA, Lim DS, Hasty P, Roth DB. Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell. 1996 Aug 9;86(3):379–389. [PubMed]
  • Beall EL, Rio DC. Drosophila IRBP/Ku p70 corresponds to the mutagen-sensitive mus309 gene and is involved in P-element excision in vivo. Genes Dev. 1996 Apr 15;10(8):921–933. [PubMed]
  • Liang F, Romanienko PJ, Weaver DT, Jeggo PA, Jasin M. Chromosomal double-strand break repair in Ku80-deficient cells. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8929–8933. [PMC free article] [PubMed]
  • Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S. p95vav associates with the nuclear protein Ku-70. Mol Cell Biol. 1996 Jan;16(1):37–44. [PMC free article] [PubMed]
  • Teo SH, Jackson SP. Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. EMBO J. 1997 Aug 1;16(15):4788–4795. [PMC free article] [PubMed]
  • Wilson TE, Grawunder U, Lieber MR. Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature. 1997 Jul 31;388(6641):495–498. [PubMed]
  • Tsukamoto Y, Kato J, Ikeda H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature. 1997 Aug 28;388(6645):900–903. [PubMed]
  • Jackson SP. Genomic stability. Silencing and DNA repair connect. Nature. 1997 Aug 28;388(6645):829–830. [PubMed]
  • Roth DB, Wilson JH. Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol Cell Biol. 1986 Dec;6(12):4295–4304. [PMC free article] [PubMed]
  • Grzesiuk E, Carroll D. Recombination of DNAs in Xenopus oocytes based on short homologous overlaps. Nucleic Acids Res. 1987 Feb 11;15(3):971–985. [PMC free article] [PubMed]
  • Chan DW, Mody CH, Ting NS, Lees-Miller SP. Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta. Biochem Cell Biol. 1996;74(1):67–73. [PubMed]
  • Maldonado E, Shiekhattar R, Sheldon M, Cho H, Drapkin R, Rickert P, Lees E, Anderson CW, Linn S, Reinberg D. A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature. 1996 May 2;381(6577):86–89. [PubMed]

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