One ring to bring them all-The role of Ku in mammalian non-homologous end joining

DNA Repair

Volumn 17, Issue , 2014, Pages 30-38

  Grundy, Gabrielle J ^a   Moulding, Hayley A ^b   Caldecott, Keith W ^a   Rulten, Stuart L ^a  

^a UNIVERSITY OF SUSSEX   (United Kingdom)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

APLF; Double strand break; Ku; Non homologous end joining; WRN

Indexed keywords

HETERODIMER; KU ANTIGEN; CELL NUCLEUS ANTIGEN; CHROMATIN; DNA BINDING PROTEIN; DNA DEPENDENT PROTEIN KINASE; DNA LIGASE;

ARTICLE; CELL SURVIVAL; CHROMATIN; DNA END JOINING REPAIR; DNA STRUCTURE; DOUBLE STRANDED DNA BREAK; MAMMAL; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; TELOMERE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; HUMAN; METABOLISM; PROTEIN CONFORMATION; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE;

ANIMALS; ANTIGENS, NUCLEAR; CHROMATIN; DNA BREAKS, DOUBLE-STRANDED; DNA END-JOINING REPAIR; DNA LIGASES; DNA-ACTIVATED PROTEIN KINASE; DNA-BINDING PROTEINS; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; TELOMERE;

EID: 84900463508     PISSN: 15687864     EISSN: 15687856     Source Type: Journal    
DOI: 10.1016/j.dnarep.2014.02.019     Document Type: Article

References (170)

1. Jeggo P.A., Kemp L.M. X-ray-sensitive mutants of Chinese hamster ovary cell line. Isolation and cross-sensitivity to other DNA-damaging agents. Mutat. Res. 1983, 112:313-327.
2. Kemp L.M., Sedgwick S.G., Jeggo P.A. X-ray sensitive mutants of Chinese hamster ovary cells defective in double-strand break rejoining. Mutat. Res. 1984, 132:189-196.
3. Taccioli G.E., Gottlieb T.M., Blunt T., Priestley A., Demengeot J., Mizuta R., Lehmann A.R., Alt F.W., Jackson S.P., Jeggo P.A. Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 1994, 265:1442-1445.
4. Casellas R., Nussenzweig A., Wuerffel R., Pelanda R., Reichlin A., Suh H., Qin X.F., Besmer E., Kenter A., Rajewsky K., Nussenzweig M.C. Ku80 is required for immunoglobulin isotype switching. EMBO J. 1998, 17:2404-2411.
5. Manis J.P., Gu Y., Lansford R., Sonoda E., Ferrini R., Davidson L., Rajewsky K., Alt F.W. Ku70 is required for late B cell development and immunoglobulin heavy chain class switching. J. Exp. Med. 1998, 187:2081-2089.
6. Indiviglio S.M., Bertuch A.A. Ku's essential role in keeping telomeres intact. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:12217-12218.
7. Myung K., Ghosh G., Fattah F.J., Li G., Kim H., Dutia A., Pak E., Smith S., Hendrickson E.A. Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. Mol. Cell Biol. 2004, 24:5050-5059.
8. Wang Y., Ghosh G., Hendrickson E.A. Ku86 represses lethal telomere deletion events in human somatic cells. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:12430-12435.
9. Woodard R.L., Lee K.J., Huang J., Dynan W.S. Distinct roles for Ku protein in transcriptional reinitiation and DNA repair. J. Biol. Chem. 2001, 276:15423-15433.
10. Lees-Miller S.P., Chen Y.R., Anderson C.W. 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, 10:6472-6481.
11. Li G., Nelsen C., Hendrickson E.A. Ku86 is essential in human somatic cells. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:832-837.
12. Takata M., Sasaki M.S., Sonoda E., Morrison C., Hashimoto M., Utsumi H., Yamaguchi-Iwai Y., Shinohara A., Takeda S. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 1998, 17:5497-5508.
13. Jeggo P.A., Kemp L.M., Holliday R. The application of the microbial tooth-pick technique to somatic cell genetics, and its use in the isolation of X-ray sensitive mutants of Chinese hamster ovary cells. Biochimie 1982, 64:713-715.
14. Nussenzweig A., Chen C., da Costa Soares V., Sanchez M., Sokol K., Nussenzweig M.C., Li G.C. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 1996, 382:551-555.
15. Ouyang H., Nussenzweig A., Kurimasa A., Soares V.C., Li X., Cordon-Cardo C., Li W., Cheong N., Nussenzweig M., Iliakis G., Chen D.J., Li G.C. Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo. J. Exp. Med. 1997, 186:921-929.
16. 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, 68:611-620.
17. Mimori T., Hardin J.A., Steitz J.A. Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. J. Biol. Chem. 1986, 261:2274-2278.
18. Jeggo P.A., Hafezparast M., Thompson A.F., Broughton B.C., Kaur G.P., Zdzienicka M.Z., Athwal R.S. Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2. Proc. Natl. Acad. Sci. U.S.A. 1992, 89:6423-6427.
19. Rathmell W.K., Chu G. Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:7623-7627.
20. Smider V., Rathmell W.K., Lieber M.R., Chu G. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science 1994, 266:288-291.
21. Doherty A.J., Jackson S.P., Weller G.R. Identification of bacterial homologues of the Ku DNA repair proteins. FEBS Lett. 2001, 500:186-188.
22. Gell D., Jackson S.P. Mapping of protein-protein interactions within the DNA-dependent protein kinase complex. Nucleic Acids Res. 1999, 27:3494-3502.
23. Osipovich O., Durum S.K., Muegge K. Defining the minimal domain of Ku80 for interaction with Ku70. J. Biol. Chem. 1997, 272:27259-27265.
24. Walker J.R., Corpina R.A., Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 2001, 412:607-614.
25. Springer T.A. Complement and the multifaceted functions of VWA and integrin I domains. Structure 2006, 14:1611-1616.
26. Xiong J.P., Li R., Essafi M., Stehle T., Arnaout M.A. An isoleucine-based allosteric switch controls affinity and shape shifting in integrin CD11b A-domain. J. Biol. Chem. 2000, 275:38762-38767.
27. Koike M., Shiomi T., Koike A. Dimerization and nuclear localization of ku proteins. J. Biol. Chem. 2001, 276:11167-11173.
28. Takeda A.A., de Barros A.C., Chang C.W., Kobe B., Fontes M.R. Structural basis of importin-alpha-mediated nuclear transport for Ku70 and Ku80. J. Mol. Biol. 2011, 412:226-234.
29. Zhang Z., Zhu L., Lin D., Chen F., Chen D.J., Chen Y. The three-dimensional structure of the C-terminal DNA-binding domain of human Ku70. J. Biol. Chem. 2001, 276:38231-38236.
30. Lehman J.A., Hoelz D.J., Turchi J.J. DNA-dependent conformational changes in the Ku heterodimer. Biochemistry 2008, 47:4359-4368.
31. Ribes-Zamora A., Mihalek I., Lichtarge O., Bertuch A.A. Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nat. Struct. Mol. Biol. 2007, 14:301-307.
32. Sawada M., Sun W., Hayes P., Leskov K., Boothman D.A., Matsuyama S. Ku70 suppresses the apoptotic translocation of Bax to mitochondria. Nat. Cell Biol. 2003, 5:320-329.
33. Schild-Poulter C., Pope L., Giffin W., Kochan J.C., Ngsee J.K., Traykova-Andonova M., Hache R.J. The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase. J. Biol. Chem. 2001, 276:16848-16856.
34. Postow L. Destroying the ring: freeing DNA from Ku with ubiquitin. FEBS Lett. 2011, 585:2876-2882.
35. Mimori T., Hardin J.A. Mechanism of interaction between Ku protein and DNA. J. Biol. Chem. 1986, 261:10375-10379.
36. Blier P.R., Griffith A.J., Craft J., Hardin J.A. Binding of Ku protein to DNA. Measurement of affinity for ends and demonstration of binding to nicks. J. Biol. Chem. 1993, 268:7594-7601.
37. Wu X., Lieber M.R. Protein-protein and protein-DNA interaction regions within the DNA end-binding protein Ku70-Ku86. Mol. Cell Biol. 1996, 16:5186-5193.
38. Yoo S., Kimzey A., Dynan W.S. Photocross-linking of an oriented DNA repair complex. Ku bound at a single DNA end. J. Biol. Chem. 1999, 274:20034-20039.
39. Lilyestrom W., van der Woerd M.J., Clark N., Luger K. Structural and biophysical studies of human PARP-1 in complex with damaged DNA. J. Mol. Biol. 2010, 395:983-994.
40. Ariumi Y., Masutani M., Copeland T.D., Mimori T., Sugimura T., Shimotohno K., Ueda K., Hatanaka M., Noda M. Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro. Oncogene 1999, 18:4616-4625.
41. Li B., Navarro S., Kasahara N., Comai L. Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1. J. Biol. Chem. 2004, 279:13659-13667.
42. Hochegger H., Dejsuphong D., Fukushima T., Morrison C., Sonoda E., Schreiber V., Zhao G.Y., Saberi A., Masutani M., Adachi N., Koyama H., de Murcia G., Takeda S. Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. EMBO J. 2006, 25:1305-1314.
43. Wang H., Rosidi B., Perrault R., Wang M., Zhang L., Windhofer F., Iliakis G. DNA ligase III as a candidate component of backup pathways of nonhomologous end joining. Cancer Res. 2005, 65:4020-4030.
44. Wang M., Wu W., Rosidi B., Zhang L., Wang H., Iliakis G. PARP-1 Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006, 34:6170-6182.
45. Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J., Baer R., Lukas J., Jackson S.P. Human CtIP promotes DNA end resection. Nature 2007, 450:509-514.
46. Pace P., Mosedale G., Hodskinson M.R., Rosado I.V., Sivasubramaniam M., Patel K.J. Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway. Science 2010, 329:219-223.
47. Dvir A., Peterson S.R., Knuth M.W., Lu H., Dynan W.S. 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, 89:11920-11924.
48. Gottlieb T.M., Jackson S.P. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell 1993, 72:131-142.
49. Hartley K.O., Gell D., Smith G.C., Zhang H., Divecha N., Connelly M.A., Admon A., Lees-Miller S.P., Anderson C.W., Jackson S.P. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell 1995, 82:849-856.
50. Kurimasa A., Kumano S., Boubnov N.V., Story M.D., Tung C.S., Peterson S.R., Chen D.J. Requirement for the kinase activity of human DNA-dependent protein kinase catalytic subunit in DNA strand break rejoining. Mol. Cell Biol. 1999, 19:3877-3884.
51. Lees-Miller S.P., Godbout R., Chan D.W., Weinfeld M., Day R.S., Barron G.M., Allalunis-Turner J. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line. Science 1995, 267:1183-1185.
52. Suwa A., Hirakata M., Takeda Y., Jesch S.A., Mimori T., Hardin J.A. DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:6904-6908.
53. West R.B., Yaneva M., Lieber M.R. Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. Mol. Cell Biol. 1998, 18:5908-5920.
54. Singleton B.K., Torres-Arzayus M.I., Rottinghaus S.T., Taccioli G.E., Jeggo P.A. The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit. Mol. Cell Biol. 1999, 19:3267-3277.
55. Rivera-Calzada A., Maman J.D., Spagnolo L., Pearl L.H., Llorca O. Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure 2005, 13:243-255.
56. Yoo S., Dynan W.S. Geometry of a complex formed by double strand break repair proteins at a single DNA end: recruitment of DNA-PKcs induces inward translocation of Ku protein. Nucleic Acids Res. 1999, 27:4679-4686.
57. DeFazio L.G., Stansel R.M., Griffith J.D., Chu G. Synapsis of DNA ends by DNA-dependent protein kinase. EMBO J. 2002, 21:3192-3200.
58. Weterings E., Verkaik N.S., Bruggenwirth H.T., Hoeijmakers J.H., van Gent D.C. The role of DNA dependent protein kinase in synapsis of DNA ends. Nucleic Acids Res. 2003, 31:7238-7246.
59. Chan D.W., Lees-Miller S.P. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J. Biol. Chem. 1996, 271:8936-8941.
60. Meek K., Douglas P., Cui X., Ding Q., Lees-Miller S.P. Trans autophosphorylation at DNA-dependent protein kinase's two major autophosphorylation site clusters facilitates end processing but not end joining. Mol. Cell Biol. 2007, 27:3881-3890.
61. Reddy Y.V., Ding Q., Lees-Miller S.P., Meek K., Ramsden D.A. Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends. J. Biol. Chem. 2004, 279:39408-39413.
62. Ding Q., Reddy Y.V., Wang W., Woods T., Douglas P., Ramsden D.A., Lees-Miller S.P., Meek K. Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol. Cell Biol. 2003, 23:5836-5848.
63. Goodarzi A.A., Yu Y., Riballo E., Douglas P., Walker S.A., Ye R., Harer C., Marchetti C., Morrice N., Jeggo P.A., Lees-Miller S.P. DNA-PK autophosphorylation facilitates Artemis endonuclease activity. EMBO J. 2006, 25:3880-3889.
64. Ma Y., Pannicke U., Schwarz K., Lieber M.R. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 2002, 108:781-794.
65. Chen L., Trujillo K., Sung P., Tomkinson A.E. Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J. Biol. Chem. 2000, 275:26196-26205.
66. Block W.D., Yu Y., Merkle D., Gifford J.L., Ding Q., Meek K., Lees-Miller S.P. Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends. Nucleic Acids Res. 2004, 32:4351-4357.
67. 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.
68. Akopiants K., Zhou R.Z., Mohapatra S., Valerie K., Lees-Miller S.P., Lee K.J., Chen D.J., Revy P., de Villartay J.P., Povirk L.F. Requirement for XLF/Cernunnos in alignment-based gap filling by DNA polymerases lambda and mu for nonhomologous end joining in human whole-cell extracts. Nucleic Acids Res. 2009, 37:4055-4062.
69. Cottarel J., Frit P., Bombarde O., Salles B., Negrel A., Bernard S., Jeggo P.A., Lieber M.R., Modesti M., Calsou P. A noncatalytic function of the ligation complex during nonhomologous end joining. J. Cell Biol. 2013, 200:173-186.
70. Ahel I., Rass U., El-Khamisy S.F., Katyal S., Clements P.M., McKinnon P.J., Caldecott K.W., West S.C. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature 2006, 443:713-716.
71. Cortes Ledesma F., El Khamisy S.F., Zuma M.C., Osborn K., Caldecott K.W. A human 5'-tyrosyl DNA phosphodiesterase that repairs topoisomerase-mediated DNA damage. Nature 2009, 461:674-678.
72. Chappell C., Hanakahi L.A., Karimi-Busheri F., Weinfeld M., West S.C. Involvement of human polynucleotide kinase in double-strand break repair by non-homologous end joining. EMBO J. 2002, 21:2827-2832.
73. Karimi-Busheri F., Lee J., Tomkinson A.E., Weinfeld M. Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'-hydroxyl termini by purified mammalian enzymes. Nucleic Acids Res. 1998, 26:4395-4400.
74. Inamdar K.V., Pouliot J.J., Zhou T., Lees-Miller S.P., Rasouli-Nia A., Povirk L.F. Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1. J. Biol. Chem. 2002, 277:27162-27168.
75. Zhou T., Akopiants K., Mohapatra S., Lin P.S., Valerie K., Ramsden D.A., Lees-Miller S.P., Povirk L.F. Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks. DNA Repair (Amst) 2009, 8:901-911.
76. Zhou T., Lee J.W., Tatavarthi H., Lupski J.R., Valerie K., Povirk L.F. Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic Acids Res. 2005, 33:289-297.
77. Suh D., Wilson D.M., Povirk L.F. 3'-Phosphodiesterase activity of human apurinic/apyrimidinic endonuclease at DNA double-strand break ends. Nucleic Acids Res. 1997, 25:2495-2500.
78. Povirk L.F., Zhou T., Zhou R., Cowan M.J., Yannone S.M. Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease. J. Biol. Chem. 2007, 282:3547-3558.
79. Yannone S.M., Khan I.S., Zhou R.Z., Zhou T., Valerie K., Povirk L.F. Coordinate 5' and 3' endonucleolytic trimming of terminally blocked blunt DNA double-strand break ends by Artemis nuclease and DNA-dependent protein kinase. Nucleic Acids Res. 2008, 36:3354-3365.
80. Clements P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P., Brenner C., Moreira M.C., Taylor A.M., Caldecott K.W. The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst) 2004, 3:1493-1502.
81. Koch C.A., Agyei R., Galicia S., Metalnikov P., O'Donnell P., Starostine A., Weinfeld M., Durocher D. Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV. EMBO J. 2004, 23:3874-3885.
82. Malu S., De Ioannes P., Kozlov M., Greene M., Francis D., Hanna M., Pena J., Escalante C.R., Kurosawa A., Erdjument-Bromage H., Tempst P., Adachi N., Vezzoni P., Villa A., Aggarwal A.K., Cortes P. Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs. J. Exp. Med. 2012, 209:955-963.
83. Soubeyrand S., Pope L., De Chasseval R., Gosselin D., Dong F., de Villartay J.P., Hache R.J. Artemis phosphorylated by DNA-dependent protein kinase associates preferentially with discrete regions of chromatin. J. Mol. Biol. 2006, 358:1200-1211.
84. Niewolik D., Pannicke U., Lu H., Ma Y., Wang L.C., Kulesza P., Zandi E., Lieber M.R., Schwarz K. DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangs. J. Biol. Chem. 2006, 281:33900-33909.
85. Roberts S.A., Strande N., Burkhalter M.D., Strom C., Havener J.M., Hasty P., Ramsden D.A. Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Nature 2010, 464:1214-1217.
86. Strande N., Roberts S.A., Oh S., Hendrickson E.A., Ramsden D.A. Specificity of the dRP/AP lyase of Ku promotes nonhomologous end joining (NHEJ) fidelity at damaged ends. J. Biol. Chem. 2012, 287:13686-13693.
87. Grundy G.J., Rulten S.L., Zeng Z., Arribas-Bosacoma R., Iles N., Manley K., Oliver A., Caldecott K.W. APLF promotes the assembly and activity of non-homologous end joining protein complexes. EMBO J. 2013, 32:112-125.
88. Shirodkar P., Fenton A.L., Meng L., Koch C.A. Identification and functional characterization of a Ku-binding motif in aprataxin polynucleotide kinase/phosphatase-like factor (APLF). J. Biol. Chem. 2013, 288:19604-19613.
89. Rossi M.L., Ghosh A.K., Bohr V.A. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair (Amst) 2010, 9:331-344.
90. Gray M.D., Shen J.C., Kamath-Loeb A.S., Blank A., Sopher B.L., Martin G.M., Oshima J., Loeb L.A. The Werner syndrome protein is a DNA helicase. Nat. Genet. 1997, 17:100-103.
91. Brosh R.M., Orren D.K., Nehlin J.O., Ravn P.H., Kenny M.K., Machwe A., Bohr V.A. Functional and physical interaction between WRN helicase and human replication protein A. J. Biol. Chem. 1999, 274:18341-18350.
92. Orren D.K., Brosh R.M., Nehlin J.O., Machwe A., Gray M.D., Bohr V.A. Enzymatic and DNA binding properties of purified WRN protein: high affinity binding to single-stranded DNA but not to DNA damage induced by 4NQO. Nucleic Acids Res. 1999, 27:3557-3566.
93. Huang S., Li B., Gray M.D., Oshima J., Mian I.S., Campisi J. The premature ageing syndrome protein, WRN, is a 3'→5' exonuclease. Nat. Genet. 1998, 20:114-116.
94. Kamath-Loeb A.S., Shen J.C., Loeb L.A., Fry M. Werner syndrome protein. II. Characterization of the integral 3'→5' DNA exonuclease. J. Biol. Chem. 1998, 273:34145-34150.
95. Cooper M.P., Machwe A., Orren D.K., Brosh R.M., Ramsden D., Bohr V.A. Ku complex interacts with and stimulates the Werner protein. Genes Dev. 2000, 14:907-912.
96. Li B., Comai L. Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein. Nucleic Acids Res. 2002, 30:3653-3661.
97. Orren D.K., Machwe A., Karmakar P., Piotrowski J., Cooper M.P., Bohr V.A. A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA. Nucleic Acids Res. 2001, 29:1926-1934.
98. Bukowy Z., Harrigan J.A., Ramsden D.A., Tudek B., Bohr V.A., Stevnsner T. WRN exonuclease activity is blocked by specific oxidatively induced base lesions positioned in either DNA strand. Nucleic Acids Res. 2008, 36:4975-4987.
99. Perry J.J., Yannone S.M., Holden L.G., Hitomi C., Asaithamby A., Han S., Cooper P.K., Chen D.J., Tainer J.A. WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nat. Struct. Mol. Biol. 2006, 13:414-422.
100. Oshima J., Huang S., Pae C., Campisi J., Schiestl R.H. Lack of WRN results in extensive deletion at nonhomologous joining ends. Cancer Res. 2002, 62:547-551.
101. Karmakar P., Piotrowski J., Brosh R.M., Sommers J.A., Miller S.P., Cheng W.H., Snowden C.M., Ramsden D.A., Bohr V.A. 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, 277:18291-18302.
102. Kusumoto R., Dawut L., Marchetti C., Wan Lee J., Vindigni A., Ramsden D., Bohr V.A. Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing. Biochemistry 2008, 47:7548-7556.
103. Yannone S.M., Roy S., Chan D.W., Murphy M.B., Huang S., Campisi J., Chen D.J. Werner syndrome protein is regulated and phosphorylated by DNA-dependent protein kinase. J. Biol. Chem. 2001, 276:38242-38248.
104. Furuse M., Nagase Y., Tsubouchi H., Murakami-Murofushi K., Shibata T., Ohta K. Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination. EMBO J. 1998, 17:6412-6425.
105. Paull T.T., Gellert M. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol. Cell 1998, 1:969-979.
106. Moreno-Herrero F., de Jager M., Dekker N.H., Kanaar R., Wyman C., Dekker C. Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 2005, 437:440-443.
107. Williams R.S., Tainer J.A. A nanomachine for making ends meet: MRN is a flexing scaffold for the repair of DNA double-strand breaks. Mol. Cell 2005, 19:724-726.
108. Falck J., Coates J., Jackson S.P. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 2005, 434:605-611.
109. Stiff T., Reis C., Alderton G.K., Woodbine L., O'Driscoll M., Jeggo P.A. Nbs1 is required for ATR-dependent phosphorylation events. EMBO J. 2005, 24:199-208.
110. Uziel T., Lerenthal Y., Moyal L., Andegeko Y., Mittelman L., Shiloh Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 2003, 22:5612-5621.
111. Goedecke W., Eijpe M., Offenberg H.H., van Aalderen M., Heyting C. Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis. Nat. Genet. 1999, 23:194-198.
112. Ma Y., Lu H., Tippin B., Goodman M.F., Shimazaki N., Koiwai O., Hsieh C.L., Schwarz K., Lieber M.R. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol. Cell 2004, 16:701-713.
113. Mahajan K.N., Nick McElhinny S.A., Mitchell B.S., Ramsden D.A. Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair. Mol. Cell Biol. 2002, 22:5194-5202.
114. DeRose E.F., Clarkson M.W., Gilmore S.A., Galban C.J., Tripathy A., Havener J.M., Mueller G.A., Ramsden D.A., London R.E., Lee A.L. Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry 2007, 46:12100-12110.
115. Mickelsen S., Snyder C., Trujillo K., Bogue M., Roth D.B., Meek K. Modulation of terminal deoxynucleotidyltransferase activity by the DNA-dependent protein kinase. J. Immunol. 1999, 163:834-843.
116. Purugganan M.M., Shah S., Kearney J.F., Roth D.B. Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase. Nucleic Acids Res. 2001, 29:1638-1646.
117. Sandor Z., Calicchio M.L., Sargent R.G., Roth D.B., Wilson J.H. Distinct requirements for Ku in N nucleotide addition at V(D)J- and non-V(D)J-generated double-strand breaks. Nucleic Acids Res. 2004, 32:1866-1873.
118. Li Z., Otevrel T., Gao Y., Cheng H.L., Seed B., Stamato T.D., Taccioli G.E., Alt F.W. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell 1995, 83:1079-1089.
119. Grawunder U., Zimmer D., Fugmann S., Schwarz K., Lieber M.R. DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol. Cell 1998, 2:477-484.
120. Costantini S., Woodbine L., Andreoli L., Jeggo P.A., Vindigni A. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK. DNA Repair (Amst) 2007, 6:712-722.
121. Drouet J., Delteil C., Lefrancois 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, 280:7060-7069.
122. Iles N., Rulten S., El-Khamisy S.F., Caldecott K.W. APLF (C2orf13) is a novel human protein involved in the cellular response to chromosomal DNA strand breaks. Mol. Cell Biol. 2007, 27:3793-3803.
123. Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A. A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 2007, 26:2094-2103.
124. Bekker-Jensen S., Fugger K., Danielsen J.R., Gromova I., Sehested M., Celis J., Bartek J., Lukas J., Mailand N. Human Xip1 (C2orf13) is a novel regulator of cellular responses to DNA strand breaks. J. Biol. Chem. 2007, 282:19638-19643.
125. Macrae C.J., McCulloch R.D., Ylanko J., Durocher D., Koch C.A. APLF (C2orf13) facilitates nonhomologous end-joining and undergoes ATM-dependent hyperphosphorylation following ionizing radiation. DNA Repair (Amst) 2008, 7:292-302.
126. Rulten S.L., Fisher A.E., Robert I., Zuma M.C., Rouleau M., Ju L., Poirier G., Reina-San-Martin B., Caldecott K.W. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol. Cell 2011, 41:33-45.
127. Buck D., Malivert L., de Chasseval R., Barraud A., Fondaneche M.C., Sanal O., Plebani A., Stephan J.L., Hufnagel M., Le Deist F., Fischer A., Durandy A., de Villartay J.P., Revy P. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 2006, 124:287-299.
128. Ahnesorg P., Smith P., Jackson S.P. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 2006, 124:301-313.
129. Lu H., Pannicke U., Schwarz K., Lieber M.R. Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity. J. Biol. Chem. 2007, 282:11155-11162.
130. Riballo E., Woodbine L., Stiff T., Walker S.A., Goodarzi A.A., Jeggo P.A. XLF-Cernunnos promotes DNA ligase IV-XRCC4 re-adenylation following ligation. Nucleic Acids Res. 2009, 37:482-492.
131. Tsai C.J., Kim S.A., Chu G. Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:7851-7856.
132. Yano K., Morotomi-Yano K., Wang S.Y., Uematsu N., Lee K.J., Asaithamby A., Weterings E., Chen D.J. Ku recruits XLF to DNA double-strand breaks. EMBO Rep. 2008, 9:91-96.
133. Jain D., Cooper J.P. Telomeric strategies: means to an end. Annu. Rev. Genet. 2010, 44:243-269.
134. Boulton S.J., Jackson S.P. Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 1996, 24:4639-4648.
135. Fattah F.J., Lichter N.F., Fattah K.R., Oh S., Hendrickson E.A. Ku70, an essential gene, modulates the frequency of rAAV-mediated gene targeting in human somatic cells. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:8703-8708.
136. Porter S.E., Greenwell P.W., Ritchie K.B., Petes T.D. The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 1996, 24:582-585.
137. Song K., Jung Y., Jung D., Lee I. Human Ku70 interacts with heterochromatin protein 1alpha. J. Biol. Chem. 2001, 276:8321-8327.
138. Song K., Jung D., Jung Y., Lee S.G., Lee I. Interaction of human Ku70 with TRF2. FEBS Lett. 2000, 481:81-85.
139. Hingorani M.M., O'Donnell M. A tale of toroids in DNA metabolism. Nat. Rev. Mol. Cell Biol. 2000, 1:22-30.
140. Feng L., Chen J. The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. Nat. Struct. Mol. Biol. 2012, 19:201-206.
141. Postow L., Funabiki H. An SCF complex containing Fbxl12 mediates DNA damage-induced Ku80 ubiquitylation. Cell Cycle 2013, 12:587-595.
142. Postow L., Ghenoiu C., Woo E.M., Krutchinsky A.N., Chait B.T., Funabiki H. Ku80 removal from DNA through double strand break-induced ubiquitylation. J. Cell Biol. 2008, 182:467-479.
143. Li G.C., Ouyang H., Li X., Nagasawa H., Little J.B., Chen D.J., Ling C.C., Fuks Z., Cordon-Cardo C. Ku70: a candidate tumor suppressor gene for murine T cell lymphoma. Mol. Cell 1998, 2:1-8.
144. Zhu C., Bogue M.A., Lim D.S., Hasty P., Roth D.B. Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell 1996, 86:379-389.
145. Finnie N.J., Gottlieb T.M., Blunt T., Jeggo P.A., Jackson S.P. 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, 92:320-324.
146. de Miranda N.F., Peng R., Georgiou K., Wu C., Sorqvist E.F., Berglund M., Chen L., Gao Z., Lagerstedt K., Lisboa S., Roos F., van Wezel T., Teixeira M.R., Rosenquist R., Sundstrom C., Enblad G., Nilsson M., Zeng Y., Kipling D., Pan-Hammarstrom Q. DNA repair genes are selectively mutated in diffuse large B cell lymphomas. J. Exp. Med. 2013, 210:1729-1742.
147. Chung U., Igarashi T., Nishishita T., Iwanari H., Iwamatsu A., Suwa A., Mimori T., Hata K., Ebisu S., Ogata E., Fujita T., Okazaki T. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J. Biol. Chem. 1996, 271:8593-8598.
148. Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.S., Ornitz D.M., Towler D.A. Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J. Biol. Chem. 2002, 277:37280-37291.
149. Wang H., Fang R., Cho J.Y., Libermann T.A., Oettgen P. Positive and negative modulation of the transcriptional activity of the ETS factor ESE-1 through interaction with p300, CREB-binding protein, and Ku 70/86. J. Biol. Chem. 2004, 279:25241-25250.
150. Hoek M., Myers M.P., Stillman B. An analysis of CAF-1-interacting proteins reveals dynamic and direct interactions with the KU complex and 14-3-3 proteins. J. Biol. Chem. 2011, 286:10876-10887.
151. Liu H., Herrmann C.H., Chiang K., Sung T.L., Moon S.H., Donehower L.A., Rice A.P. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. Biochem. Biophys. Res. Commun. 2010, 397:245-250.
152. Raval P., Kriatchko A.N., Kumar S., Swanson P.C. Evidence for Ku70/Ku80 association with full-length RAG1. Nucleic Acids Res. 2008, 36:2060-2072.
153. Li B., Comai L. Functional interaction between Ku and the werner syndrome protein in DNA end processing. J. Biol. Chem. 2000, 275:39800.
154. Wei L., Lan L., Hong Z., Yasui A., Ishioka C., Chiba N. Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol. Cell Biol. 2008, 28:7380-7393.
155. Parvathaneni S., Stortchevoi A., Sommers J.A., Brosh R.M., Sharma S. Human RECQ1 interacts with Ku70/80 and modulates DNA end-joining of double-strand breaks. PLoS ONE 2013, 8:e62481.
156. Spagnolo L., Barbeau J., Curtin N.J., Morris E.P., Pearl L.H. Visualization of a DNA-PK/PARP1 complex. Nucleic Acids Res. 2012, 40:4168-4177.
157. Shahi A., Lee J.H., Kang Y., Lee S.H., Hyun J.W., Chang I.Y., Jun J.Y., You H.J. Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair. Nucleic Acids Res. 2011, 39:2130-2143.
158. Mazumder S., Plesca D., Kinter M., Almasan A. Interaction of a cyclin E fragment with Ku70 regulates Bax-mediated apoptosis. Mol. Cell Biol. 2007, 27:3511-3520.
159. Huang J., Nueda A., Yoo S., Dynan W.S. 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, 272:26009-26016.
160. Matheos D., Ruiz M.T., Price G.B., Zannis-Hadjopoulos M. Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication. Biochim. Biophys. Acta 2002, 1578:59-72.
161. Kinner A., Wu W., Staudt C., Iliakis G. Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 2008, 36:5678-5694.
162. New M., Olzscha H., Liu G., Khan O., Stimson L., McGouran J., Kerr D., Coutts A., Kessler B., Middleton M., La Thangue N.B. A regulatory circuit that involves HR23B and HDAC6 governs the biological response to HDAC inhibitors. Cell Death Differ. 2013, 20:1306-1316.
163. Subramanian C., Jarzembowski J.A., Opipari A.W., Castle V.P., Kwok R.P. HDAC6 deacetylates Ku70 and regulates Ku70-Bax binding in neuroblastoma. Neoplasia 2011, 13:726-734.
164. Li P., Gao S., Wang L., Yu F., Li J., Wang C., Wong J. ABH2 couples regulation of ribosomal DNA transcription with DNA alkylation repair. Cell Rep. 2013, 4:817-829.
165. Aravind L., Koonin E.V. Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. Genome Res. 2001, 11:1365-1374.
166. Palmbos P.L., Daley J.M., Wilson T.E. Mutations of the Yku80C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining. Mol. Cell Biol. 2005, 25:10782-10790.
167. Couto C.A., Wang H.Y., Green J.C., Kiely R., Siddaway R., Borer C., Pears C.J., Lakin N.D. PARP regulates nonhomologous end joining through retention of Ku at double-strand breaks. J. Cell Biol. 2011, 194:367-375.
168. Rivera-Calzada A., Spagnolo L., Pearl L.H., Llorca O. Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Rep. 2007, 8:56-62.
169. Harris R., Esposito D., Sankar A., Maman J.D., Hinks J.A., Pearl L.H., Driscoll P.C. The 3D solution structure of the C-terminal region of Ku86 (Ku86CTR). J. Mol. Biol. 2004, 335:573-582.
170. Zhang Z., Hu W., Cano L., Lee T.D., Chen D.J., Chen Y. Solution structure of the C-terminal domain of Ku80 suggests important sites for protein-protein interactions. Structure 2004, 12:495-502.