The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination

DNA Repair

Volumn 3, Issue 8-9, 2004, Pages 817-826

  Lieber, Michael R ^a   Ma, Yunmei ^a   Pannicke, Ulrich ^b   Schwarz, Klaus ^b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF ULM   (Germany)

Author keywords

Artemis; DNA ligase IV; DNA dependent protein kinase; DNA PKcs; Double strand break repair; Genetic recombination; Immunoglobulin gene recombination; Ku; Ku70; Ku86; RAG 1; RAG 2; Recombination activating genes; V(D)J recombination; XRCC4

Indexed keywords

DNA; DOUBLE STRANDED DNA; LYMPHOCYTE ANTIGEN RECEPTOR; POLYDEOXYRIBONUCLEOTIDE SYNTHASE;

CELL CULTURE; DNA CLEAVAGE; DNA DAMAGE; DNA RECOMBINATION; DNA REPAIR; DNA STRAND BREAKAGE; EUKARYOTIC CELL; HOMOLOGOUS RECOMBINATION; HUMAN; IMMUNOGLOBULIN GENE; IONIZING RADIATION; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; VERTEBRATE; YEAST;

ANIMALS; DNA DAMAGE; DNA REPAIR; HUMANS; IMMUNOGLOBULINS; LYMPHOCYTES; MODELS, BIOLOGICAL; MODELS, GENETIC; OXYGEN; RECOMBINATION, GENETIC; VDJ RECOMBINASES;

EUKARYOTA; VERTEBRATA;

EID: 3242879122     PISSN: 15687864     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.dnarep.2004.03.015     Document Type: Review

References (81)

1. Ward J.F. Complexity of damage produced by ionizing radiation. Cold Spring Harb. Symp. Quant. Biol. 65:2000;377-382
2. Imlay J.A., Linn S. DNA damage and oxygen radical toxicity. Science. 240:1988;1302-1309
3. Karanjawala Z.E., Murphy N., Hinton D.R., Hsieh C.-L., Lieber M.R. Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in double-strand break repair mutants. Curr. Biol. 12:2002;397-402
4. Lieber M.R., Ma Y., Pannicke U., Schwarz K. Mechanism and regulation of human non-homologous DNA end-joining. Nat. Rev. Mol. Cell. Biol. 4:2003;712-720
5. West S.C. Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell. Biol. 4:2003;435-445
6. 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. 17:1998;5497-5508
7. 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. 412:2001;607-614
8. Falzon M., Fewell J., Kuff E.L. EBP-80, a transcription factor closely resembling the human autoantigen Ku. Recognizes single- to double-strand transitions in DNA. J. Biol. Chem. 268:1993;10546-10552
9. Moshous D., Callebaut I., Chasseval R.d., Corneo B., Cavazzana-Calvo M., Diest F.L., Tezcan I., Sanal O., Bertrand Y., Philippe N., Fischer A., Villartay J.-P.d. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell. 105:2001;177-186
10. Ma Y., Pannicke U., Schwarz K., Lieber M.R. Hairpin opening and overhang processing by an Artemis:DNA-PKcs complex in V(D)J recombination and in nonhomologous end joining. Cell. 108:2002;781-794
11. C.W. Anderson, T.H. Carter, The DNA-activated protein kinase-DNA-PK, in: R. Jessberger, M.R. Lieber (Eds.), Molecular Analysis of DNA Rearrangements in the Immune System, Springer-Verlag, Heidelberg, 1996, pp. 91-112.
12. Gottlieb T., Jackson S.P. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 72:1993;131-142
13. Yaneva M., Kowalewski T., Lieber M.R. Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy. EMBO J. 16:1997;5098-5112
14. West R.B., Yaneva M., Lieber M.R. Productive and Nonproductive Complexes of Ku and DNA-PK at DNA Termini. Mol. Cell. Biol. 18:1998;5908-5920
15. 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. 275:2000;26196-26205
16. NickMcElhinny S.A., Snowden C.M., McCarville J., Ramsden D.A. Ku recruits the XRCC4-ligase IV complex to DNA ends. Mol. Cell. Biol. 20:2000;2996-3003
17. Grawunder U., Wilm M., Wu X., Kulesza P., Wilson T.E., Mann M., Lieber M.R. Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells. Nature. 388:1997;492-495
18. Wilson T.E., Grawunder U., Lieber M.R. Yeast DNA ligase IV mediates non-homologous DNA end joining. Nature. 388:1997;495-498
19. Schar P., Herrmann G., Daly G., Lindahl T. A newly identified DNA ligase of S. cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev. 11:1997;1912-1924
20. Teo S.H., Jackson S.P. Identification of S. cerevisiae DNA ligase IV: involvement in DNA double-strand break repair. EMBO J. 16:1997;4788-4795
21. Yu K., Lieber M.R. Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism. DNA Repair. 2:2003;1163-1174
22. Lewis S.M. The mechanism of V(D)J joining: lessons from molecular immunological and comparative analyses. Adv. Immunol. 56:1994;27-150
23. Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu. Rev. Biochem. 71:2002;101-132
24. Fugmann S.D., Lee A.I., Shockett P.E., Villey I.J., Schatz D.G. The RAG proteins and V(D)J recombination: complexes, ends, and transposition. Ann. Rev. Immunol. 18:2000;495-527
25. Chu G. Double-strand break repair. J. Biol. Chem. 272:1997;24097-24100
26. 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. 86:1996;379-389
27. Nicolas N., Moshous D., Cavazzana-Calvo M., Papadoupoulo D., Chasseval R.d., Deist F.L., Fischer A., Villartay J.-P.d. A human severe combined immunodeficiency condition with increased sensitivity to ionizing radiation and impaired V(D)J rearrangements defines a new DNA recombination/repair deficiency. J. Exp. Med. 188:1998;627-634
28. Lieber M.R., Hesse J.E., Lewis S., Bosma G.C., Rosenberg N., Mizuuchi K., Bosma M.J., Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 55:1988;7-16
29. McBlane J.F., Gent D.C.v., Ramsden D.A., Romeo C., Cuomo C.A., Gellert M., Oettinger M.A. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell. 83:1995;387-395
30. vanGent D.C., Mizuuchi K., Gellert M. Similarities between initiation of V(D)J recombination and retroviral integration. Science. 271:1996;1592-1594
31. Ramsden D.A., 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. 17:1998;609-614
32. DeFazio L.G., Stansel R.M., Griffith J.D., Chu G. Synapsis of DNA ends by DNA-dependent protein kinase. EMBO J. 21:2002;3192-3200
33. Suwa A., Hirakata M., Takeda Y., Jesch S., 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. 91:1994;6904-6908
34. Chan D.W., Lees-Miller S.P. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J. Biol. Chem. 271:1996;8936-8941
35. Chan D.W., Mody C.H., Ting N.S., Lees-Miller S.P. Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta. Biochem. Cell Biol. 74:1996;67-73
36. Ma Y., Lieber M.R. Binding of inositol hexakisphosphate (IP6) to Ku but Not to DNA-PKcs. J. Biol. Chem. 277:2002;10756-10759
37. deVries E., vanDriel W., Bergsma W.G., Arnberg A.C., vanderVliet P.C. HeLa nuclear protein recognizing DNA termini and translocating on DNA forming a regular DNA-multimeric protein complex. J. Mol. Biol. 208:1989;65-78
38. Boskovic J., Rivera-Calzada A., Maman J., Chacon P., Willison K., Pearl L., Llorca O. Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J. 22:2003;5875-5882
39. Merkle D., Douglas P., Moorhead G.B., Leonenko Z., Yu Y., Cramb D., Bazett-Jones D.P., Lees-Miller S.P. The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by, phosphorylation. Biochemistry. 41:2002;1206-1221
40. Ding O., Reddy Y., 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. 23:2003;5836-5848
41. Wilson T., Lieber M.R. Efficient processing of DNA ends during yeast nonhomologous end joining: evidence for a DNA polymerase beta (POL4)-dependent pathway. J. Biol. Chem. 274:1999;23599-23609
42. Tseng H.M., Tomkinson A.E. A physical and functional interaction between yeast Pol4 and Dnl4-Lif1 links DNA synthesis and ligation in nonhomologous end joining. J. Biol. Chem. 277:2002;45630-45637
43. Mahajan K.N., NickMcElhinny S.A., Mitchell B.S., Ramsden D.A. Association of DNA polymerase mu with Ku and DNA ligase IV: role of in end-joining double-strand break repair. Mol. Cell. Biol. 22:2002;5194-5202
44. Bertocci B., Smet A.D., Flatter E., Dahan A., Bories J., Landreau C., Weill J.C., Reynaud C.A. DNA polymerases mu and lambda are dispensible for Ig gene hypermutation. J. Immunol. 168:2002;3702-3706
45. Bertocci B., Smet A.D., Berek C., Weill J.-C., Reynaud C.-A. Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu. Immunity. 19:2003;203-211
46. Lee J.W., Blanco L., Zhou T., Garcia-Diaz M., Bebenek K., Kunkel T.A., Wang Z., Povirk L.F. Implication of DNA polymerase lambda in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts. J. Biol. Chem. 279:2004;805-811
47. Agrawal A., Schatz D.G. RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination. Cell. 89:1997;43-53
48. Hiom K., Gellert M. A stable RAG1-RAG2-DNA complex that is active in V(D)J cleavage. Cell. 88:1997;65-72
49. Bollum F.J. Calf thymus polymerase. J. Biol. Chem. 235:1960;2399-2403
50. A. Kornberg, T. Baker, DNA Replication, second ed. W.H. Freeman, New York, 1992.
51. Gauss G.H., Lieber M.R. Mechanistic constraints on diversity in human V(D)J recombination. Mol. Cell. Biol. 16:1996;258-269
52. Lieber M.R. Site-specific recombination in the immune system. FASEB J. 5:1991;2934-2944
53. Lieber M.R., Hesse J.E., Mizuuchi K., Gellert M. Lymphoid V(D)J recombination: nucleotide insertion at signal joints as well as coding joints. Proc. Natl. Acad. Sci. 85:1988;8588-8592
54. Gu Y., Seidl K., Rathbun G.A., Zhu C., Manis J.P., vanderStoep, N., Davidson L., Cheng H.L., Sekiguchi J., Frank K., Stanhope-Baker P., Schlissel M.S., Roth D.B., Alt F.W. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 7:1997;653-665
55. Ouyang H., Nussenzweig A., Kurimasa A., Soares V., 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. 186:1997;921-929
56. Imlay J.A. How oxygen damages microbes: oxygen tolerance and obligate anaerobiosis. Adv. Microb. Physiol. 46:2002;111-153
57. Wang H., Perrault A.R., Takeda Y., Qin W., Wang H., Iliakis G. Biochemical evidence for Ku-independent backup pathways for NHEJ. Nucl. Acids Res. 31:2003;5377-5388
58. Udayakumar D., Bladen C.L., Hudson F.Z., Dynan W.S. Distinct pathways of nonhomologous end joining that are differentially regulated by DNA-dependent protein kinase-mediated phosphorylation. J. Biol. Chem. 278:2003;1631-1635
59. Harfst E., Cooper S., Neubauer S., Distel L., Grawunder U. Normal V(D)J recombination in cells from patients with Nijmegen breakage syndrome. Mol. Immunol. 37:2000;915-929
60. Yeo T.C., Xia D., Hassouneh S., Yang X.O., Sabath D.E., Sperling K., Gatti R.A., Concannon P., Willerford D.M. V(D)J rearrangement in Nijmegen breakage syndrome. Mol. Immunol. 37:2000;1131-1139
61. Bender C.F., Sikes M.L., Sullivan R., Huye L.E., Beau M.M.L., Roth D.B., Mirzoeva O.K., Oltz E.M., Petrini J.H. Cancer predisposition and hematopoietic failure in Rad50(S/S) mice. Genes Dev. 16:2002;2237-2251
62. Verkaik N.S., Lange R.E.-v., Heemst D.v., Bruggenwirth H., Hoeijmakers J.H., Mz M.Z.Z., Gent D.C.v. Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells. Eur. J. Immunol. 32:2002;701-709
63. vanHeemst D., Brugmans L., Verkaik N., vanGent D.C. End-joining of blunt DNA double-strand breaks in mammalian fibroblasts is precise and requires DNA-PK and XRCC4. DNA Repair. 3:2004;43-50
64. Ma J.L., Kim E.M., Haber J.E., Lee S.E. Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol. Cell. Biol. 23:2003;8820-8828
65. E.C. Friedberg, G.C. Walker, W. Siede, DNA Repair and Mutagenesis, ASM Press, Washington, DC, 1995.
66. Frank K.M., Sharpless N.E., Gao Y., Sekiguchi Y.M., Ferguson D.O., Zhu C., Manis J.P., Horner J., DePinho R., Alt F.W. DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. Mol. Cell. 5:2000;993-1002
67. Milne G.T., Jin S., Shannon K.B., Weaver D.T. Mutations in two Ku homologs define a DNA end-joining repair pathway in S. cerevisiae. Mol. Cell. Biol. 16:1996;4189-4198
68. Boulton S.J., Jackson S.P. S. cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO J. 15:1996;5093-5103
69. Moore J.K., Haber J.E. Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in S. cerevisiae. Mol. Cell. Biol. 16:1996;2164-2173
70. Mills K.D., Ferguson D.O., Alt F.W. The role of DNA breaks in genomic instability and tumorigenesis. Immunol. Rev. 194:2003;77-95
71. O'Driscoll M., Cerosaletti K.M., Girard P.M., Dai T., Stumm M., Kysela B., Hirsch B., Gennery A., Palmer S.E., Seidel J., Gatti R.A., Varon R., Oettinger M.A., Neitzel H., Jeggo P.A., Concannon P. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol. Cell. 8:2001;1175-1185
72. Karanjawala Z.E., Grawunder U., Hsieh C.-L., Lieber M.R. The nonhomologous DNA end joining pathway is important for chromosome stability in primary fibroblasts. Curr. Biol. 9:1999;1501-1504
73. Li G., Nelsen C., Hendrickson E.A. Ku86 is essential in human somatic cells. Proc. Natl. Acad. Sci. 99:2002;832-837
74. Sharpless N.E., Ferguson D.O., O'Hagen R., Castrillon D., Lee C., Farazi P., Alson S., Fleming J., Morton C., Frank K., Chin L., Alt F.W., DePinho R.A. Impaired nonhomologous DNA end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions. Mol. Cell. 8:2001;1187-1196
75. Chen H.T., Bhandoola A., Difilippantonio M.J., Zhu J., Brown M., Tai X., Rogakou E.P., Brotz T.M., Bonner W.M., Ried T., Nussenzweig A. Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX. Science. 290:2000;1962-1965
76. Bassing C.H., Suh H., Ferguson D.O., Chua K.F., Manis J., Eckersdorff M., Bronson R., Lee C., Alt F.W., Histone H2AX: a dosage-dependent suppress of oncogenic translocations and tumors. Cell. 114:2003;359-370
77. Celeste A., Difilippantonio S., Difilippantonio M.J., Fernandez-Capetillo O., Pilch D.R., Sedelnikova O.A., Eckhaus M., Ried T., Bonner W.M., Nussenzweig A. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell. 114:2003;371-383
78. Celeste A., Fernandez-Capetillo O., Kruhlak M.J., Pilch D.R., Staudt D.W., Lee A., Bonner R.F., Bonner W.M., Nussenzweig A. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat. Cell Biol. 5:2003;675-679
79. Bennett C.B., Lewis A.L., Baldwin K.K., Resnick M.A. Lethality induced by a single site-specific double-strand break in a dispensible yeast plasmid. Proc. Natl. Acad. Sci. 90:1993;5613-5617
80. Dai Y., Kysela B., Hanakahi L.A., Manolis K., Riballo E., Stumm M., Harville T.O., West S.C., Oettinger M.A., Jeggo P.A. Nonhomologous end joining and V(D)J recombination require an additional factor. Proc. Natl. Acad. Sci. 100:2003;2462-2467
81. Modesti M., Junop M.S., Ghirlando R., Rakt M.d.v., Gellert M., Yang W., Kanaar R. Tetramerization and DNA ligase IV interaction of the DNA double-strand break protein XRCC4 are mutually exclusive. J. Mol. Biol. 334:2003;215-228