The DNA-dependent protein kinase: A matter of life and (cell) death

Current Opinion in Cell Biology

Volumn 8, Issue 3, 1996, Pages 325-330

  McConnell, Kevin ^a   Dynan, William S ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; DNA BINDING PROTEIN; MUTANT PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE;

APOPTOSIS; AUTOIMMUNITY; DNA RECOMBINATION; DNA REPAIR; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME STRUCTURE; ENZYME SUBUNIT; IMMUNOGLOBULIN GENE; PRIORITY JOURNAL; RADIOSENSITIVITY; SHORT SURVEY; STRESS; T LYMPHOCYTE RECEPTOR GENE;

EID: 0029888569     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(96)80005-6     Document Type: Article

References (54)

1. Walker Al, Hunt T, Jackson RJ, Andersen 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, 4:139-145.
2. 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 USA 1992, 89:11920-11924.
3. Gottlieb TM, Jackson SP: The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell 1993, 72:131-142.
4. 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 USA 1994, 91:6904-6908.
5. 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, 264:13407-13411.
6. Reeves W, Sthoeger ZM: Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J Biol Chem 1989, 264:5047-5052.
7. 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 USA 1990, 87:1777-1781.
8. Chan JYC, Lerman Ml, Prabhakar BX, 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, 264:3651-3654.
9. •].
10. •].
11. Feldmann H, Winnacker EL: A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae. J Biol Chem 1993, 268:12895-12900.
12. Jackson SP, Hartley KO, Gell D, Smith GCM, Zhang H, Divecha N, Connelly MA, Adman A, Lees-Miller SP, Anderson CW: DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the Ataxia Telanglectasia gene product Cell 1995, 82:849-856. Reveals the long-awaited cDNA sequence for the catalytic DNA-PK subunit. About 90% of the sequence does not match any known protein. The remaining 10% corresponds to the carboxy-terminal kinase domain of DNA-PK, and identifies a DNA-PK as a member of a newly defined subgroup of potential protein kinases within the PI3K superfamily.
13. ••] could represent an additional exon.
14. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S et al.: A single ataxia telangiectasia gene with a product similar to P1-3 kinase. Science 1995, 268:1749-1753-A singularly important paper to researchers in the AT field because it defines a single, causative gene for the disease. This discovery is significant in the context of this review because of the sequence similarity between the kinase domains in ATM and in the DNA-PK catalytic subunit.
15. Hunter T: When is a lipid kinase not a lipid kinase? When it is a protein kinase. Cell 1995, 83:1-4. A current compilation of members of the PI3K gene family, together with what is known of their functions.
16. Anderson CW: DNA damage and the DNA-activated protein kinase. Trends Biochem Sci 1993, 18:433-437.
17. Jeggo PA, Thompson LH: Nomenclature of human genes involved in ionizing radiation sensitivity. Mutat Res 1995, 337:131-134. A useful guide to the arcane nomenclature used in the DNA-repair field.
18. ••].
19. Getts RC, Stamato TD: Absence of Ku-like DNA end binding activity in the xrs double-strand DNA repair-deficient mutant. J Biol Chem 1994, 269:15981-15984. Earliest report of the absence of Ku activity in a repair-deficient mutant cell line.
20. 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, 266:288-291. One of several contemporaneous papers describing the absence of Ku86 in repair-deficient cells and complementation by Ku86 cDNA.
21. Rathmell WK, Chu G: Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc Natl Acad Sci USA 1994, 91:7623-7627. Describes the absence of Ku86 in repair-deficient cells.
22. 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 USA 1995, 92:320-324. Shows that DNA-PK activity, in addition to the Ku protein, is absent from repair-deficient mutants. Describes a novel solid-phase assay for DNA-PK activity.
23. Taccioli GE, Rathbun G, Oltz E, Stamato T, Jeggo PA, Alt FW: Impairment of V(D)J recombination in double-strand break repair mutants. Science 1993, 260:207-210.
24. ••].
25. Lees-Miller SP, Godbout R, Chan DW, Weinfeld M, Day RS, Barron GM, Allalanis-Turner J: Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 1995, 267:1183-1185. One of several contemporaneous papers describing the absence of the DNA-PK catalytic subunit from repair-deficient cells. Provides the only example thus far of catalytic subunit deficiency in a cell line of human origin.
26. 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, 267:1178-1183. One of several contemporaneous papers describing the absence of the DNA-PK catalytic subunit from XRCC/scid cells, and the complementation of this missing subunit by DNA from human chromosome 8. Includes extensive genetic mapping studies.
27. Blunt T, Finnie NJ, Taccioli GE, Smith GCM, Demengeot J, Gottlieb TM, Mizuta R, Varghese AJ, Alt FW, Jeggo PA, Jackson SP: 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, 80:813-823. One of several contemporaneous papers describing the absence of the DNA-PK catalytic subunit from XRCC7/scid cells. Demonstrates complementation in these cells with a yeast artificial chromosome that spans the DNA-PK catalytic subunit structural locus, providing the most direct evidence to date that the scid defect is found in or near the DNA-PK catalytic subunit structural gene.
28. Gellert M: DNA double-strand breaks and hairpins in V(D)J recombination. Semin Immunol 1994, 6:125-130. A useful introduction to the complex topic of V(D)J recombination, accessible to the non-specialist.
29. McBlane JF, Van Gent DC, Ramsden DA, Romeo C, Cuomo CA, Gellert M, Oettinger MA: Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell 1995, 83:387-396.
30. Cao QP, Pitt S, Leszyk J, Baril EF: DNA-dependent ATPase from HeLa cells Is related to human Ku autoantigen. Biochemistry 1994, 33:8548-8557. Provides extensive biochemical evidence for a DNA-dependent ATPase that is closely associated with, and apparently intrinsic to, the Ku protein.
31. 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 Ku autoantigen. EMBO J 1994, 13:4991-5001. Provides extensive biochemical evidence for an ATP-dependent helicase activity, which is characterized by unusual substrate preference. The activity is closely associated with, and apparently intrinsic to, the Ku protein.
32. Jeggo PA, Taccioli GE, Jackson SP: Ménage à trois: double strand break repair, V(D)J recombination and DNA-PK. Bioessays 1995, 17:949-957.
33. 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, 270:1449-1454. Provides biochemical evidence that DNA-PK is directly stimulated by HSF1, the transcription factor that serves as a master regulator of the heat-shock response. Stimulation is also seen with a fragment of the yeast Gal4 protein which is present in many laboratory fusion proteins (the significance of this stimulation is unclear), but is not seen with typical acidic transcriptional activators.
34. Peterson SR, Dvir A, Anderson CW, Dynan WS: DNA binding provides a signal for phosphorylation of the RNA polymerase II heptapeptide repeats. Genes Dev 1992, 6:426-438. Demonstrates the ability of DNA-PK to carry out regulated phosphorylation of the carboxy-terminal domain of RNA polymerase II.
35. O'Brien T, Hardin S, Greenleaf A, Lis JT: Phosphorylation of RNA polymerase II C-terminal domain and transcriptional elongation. Nature 1994, 370:75-77. The most recent in an elegant series of papers which dissect the molecular events that occur during Drosophila heat shock gene induction.
36. Kim D, Li C: A constitutive heat shock element-binding factor is immunologically identical to the Ku autoantigen. J Biol Chem 1995, 270:15277-15284, Demonstrates that the Ku protein is identical to a heat shock element binding factor that was defined by this group in earlier work. The sequence specificity of Ku protein binding to the heat-shock element is not addressed.
37. Li G: Suppression of heat-induced hsp70 expression by the 70-kDa subunit of the human Ku autoantigen. Proc Natl Acad Sci USA 1995, 92:4512-4516. Overexpression of Ku70 is shown to interfere with hsp70 induction. The authors favor a model in which there is direct competition between the Ku protein and HSF1 for binding to a common DNA site, but the data are also consistent with competition between the Ku protein and HSF1 for limiting amounts of the DNA-PK catalytic subunit, as discussed in the text of this review.
38. Ben-Hur E, Elkind MM, Bronk BV: Thermally enhanced radioresponse of cultured Chinese hamster cells: Inhibition of repair of sublethal damage and enhancement of lethal damage. Radiat Res 1974, 58:38-51.
39. Robinson JE, Wizenberg MJ: Thermal sensitivity and the effect of elevated temperatures on the radiation sensitivity of Chinese Hamster cells. Acta Radiol 1974, 13:241-248.
40. O'Hara M: Thermal response and hyperthermic radiosensitization of scid mouse bone marrow CFU-C. Int J Radiat Oncol Biol Phys 1995, 31:905-910. Shows that scid mouse bone marrow cells mount some degree of heat-shock response, but are incapable of thermal radiosensitization.
41. 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, 182:1625-1634. Provides the first report of the cleavage of the DNA-PK catalytic subunit during induced apoptosis. The authors favor a model different from the one proposed by us in this review; in their model, cleavage exposes new epitopes on DNA-PK that serve as targets for an autoimmune response.
42. Ajmani AK, Satoh M, Reap E, Cohen PL, Reeves WH: Absence of autoantigen Ku In mature human neutrophils and human promyelocytic leukemia line (HL-60) cells and lymphocytes undergoing apoptosis. J Exp Med 1995, 181:2049-2058. Demonstrates the absence of the Ku protein in certain apoptotic cell populations.
43. Mimori T, Skizuki 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, 68:611-620.
44. Yaneva M, Arnett EC: Antibodies against Ku protein in sera from patients with autoimmune diseases. Clin Exp Immunol 1989, 76:366-372.
45. Reeves WH: Use of monoclonal antibodies for the characterization of novel DNA-binding proteins recognized by human autoimmune sera. J Exp Med 1985, 161:18-39.
46. Suwa A, Hirakata M, Takeda Y, Okano U, Mimori T, Inada S, Watanabe F, Teraoka H, Dynan WS, Hardin JA: Autoantibodies to DNA-dependent protein kinase: probes for the catalytic subunit. J Clin Invest 1996, 97:1417-1421.
47. Abendroth FD, Peterson SR, Galman M, Suwa A, Hardin JA, Dynan WS: Identification of human autoantibodies to transcription factor IIB. Nucleic Acids Res 1995, 23:2770-2774.
48. Matzinger P: Tolerance, danger, and the extended family. Annu Rev Immunol 1994, 12:991-1045.
49. Le Romancer ML, Reyl-Desmars F, Cherifi Y, Pigeon C, Bottari S, Meyer O, Lewin MJM: The 86-kDa subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity. J Biol Chem 1994, 269:17464-17468. An initial report describing somatostatin receptor like activity in the Ku protein; it is not yet clear how this activity fits in with the other known functions of the Ku protein.
50. Romero F: p95vav associates with the nuclear protein Ku-70. Mol Cell Biol 1996, 16:37-44. A very recent report which shows that the vav protooncogene product binds Ku70.
51. Labhart P: DNA-dependent protein kinase specifically represses promoter-directed transcription initiation by RNA polymerase I. Proc Natl Acad Sci USA 1995, 92:2934-2938.
52. Kuhn A, Gottlieb TM, Jackson SP, Grummt I: DNA-dependent protein kinase: a potent inhibitor of transcription by RNA polymerase I. Genes Dev 1995, 9:193-203.
53. 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, 202:736-742.
54. Boubnov NV, Weaver DT: Scid cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase. Mol Cell Biol 1995, 15:5700-5706.