Mechanisms that promote and suppress chromosomal translocations in lymphocytes

Annual Review of Immunology

Volumn 29, Issue , 2011, Pages 319-350

  Gostissa, Monica ^a   Alt, Frederick W ^a   Chiarle, Roberto ^a,b  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b UNIVERSITY OF TURIN   (Italy)

Author keywords

antigen receptor genes; DNA double strand breaks; DSB repair; lymphoma; nonhomologous end joining

Indexed keywords

ATM PROTEIN; IMMUNOGLOBULIN HEAVY CHAIN; LYMPHOCYTE ANTIGEN RECEPTOR; RAG1 PROTEIN; RAG2 PROTEIN;

ARTICLE; B LYMPHOCYTE; CHROMOSOME; CHROMOSOME PAIRING; CHROMOSOME TRANSLOCATION; DOUBLE STRANDED DNA BREAK; GENE AMPLIFICATION; GENE LOCUS; HUMAN; LYMPHOCYTE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE;

ANIMALS; CYTIDINE DEAMINASE; DNA BREAKS, DOUBLE-STRANDED; GENE REARRANGEMENT, B-LYMPHOCYTE; HUMANS; LEUKEMIA; LYMPHOCYTES; LYMPHOMA; TRANSLOCATION, GENETIC;

EID: 79953032797     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-031210-101329     Document Type: Article

References (176)

1. K̈uppers R, Dalla-Favera R. 2001. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20, 5580-94.
2. Mitelman F, Johansson B, Mertens F. 2007. The impact of translocations and gene fusions on cancer causation. Nat. Rev. Cancer 7:233-45. (Pubitemid 46480968)
3. Difilippantonio MJ, Petersen S, Chen HT, Johnson R, Jasin M, et al. 2002. Evidence for replicative repair of DNA double-strand breaks leading to oncogenic translocation and gene amplification. J. Exp. Med. 196:469-80.
4. Zhu C, Mills KD, Ferguson DO, Lee C, Manis J, et al. 2002. Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell 109:811-21. (Pubitemid 34785997)
5. Mahowald GK, Baron JM, Mahowald MA, Kulkarni S, Bredemeyer AL, et al. 2009. Aberrantly resolved RAG-mediated DNA breaks in Atm-deficient lymphocytes target chromosomal breakpoints in cis. Proc. Natl. Acad. Sci. USA 106:18339-44.
6. Zarrin AA, Del Vecchio C, Tseng E, Gleason M, Zarin P, et al. 2007. Antibody class switching mediated by yeast endonuclease-generated DNA breaks. Science 315:377-81. (Pubitemid 46175518)
7. Lieber MR. 2010. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 79:181-211.
8. Franco S, Alt FW, Manis JP. 2006. Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations. DNA Repair 5:1030-41. (Pubitemid 44308467)
9. Gostissa M, Ranganath S, Bianco JM, Alt FW. 2009. Chromosomal location targets different MYC family gene members for oncogenic translocations. Proc. Natl. Acad. Sci. USA 106:2265-70.
10. Honjo T, Alt FW, Neuberger M. 2004. Molecular Biology of B Cells. London: Elsevier Acad. 589 pp.
11. Oettinger MA, Schatz DG, Gorka C, Baltimore D. 1990. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 248:1517-23.
12. Schatz DG, Oettinger MA, Baltimore D. 1989. The V(D)J recombination activating gene, RAG-1. Cell 59:1035-48.
13. van Gent DC, McBlane JF, Ramsden DA, Sadofsky MJ, Hesse JE, Gellert M. 1995. Initiation of V(D)J recombination in a cell-free system. Cell 81:925-34.
14. Taccioli GE, Rathbun G, Oltz E, Stamato T, Jeggo PA, Alt FW. 1993. Impairment of V(D)J recombination in double-strand break repair mutants. Science 260:207-10. (Pubitemid 23140884)
15. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, PapaioannouVE. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68:869-77.
16. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, et al. 1992. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855-67.
17. Rooney S, Chaudhuri J, Alt FW. 2004. The role of the non-homologous end-joining pathway in lymphocyte development. Immunol. Rev. 200:115-31. (Pubitemid 38998197)
18. Jung D, Giallourakis C, Mostoslavsky R, Alt FW. 2006. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu. Rev. Immunol. 24:541-70.
19. Fugmann SD, Lee AI, Shockett PE, Villey IJ, Schatz DG. 2000. The RAG proteins and V(D)J recombination: complexes, ends, and transposition. Annu. Rev. Immunol. 18:495-527. (Pubitemid 30365389)
20. Agrawal A, Eastman QM, Schatz DG. 1998. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394:744-51. (Pubitemid 28391631)
21. Hiom K, Melek M, Gellert M. 1998. DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell 94:463-70. (Pubitemid 28391862)
22. Tsai AG, Lieber MR. 2010. Mechanisms of chromosomal rearrangement in the human genome. BMC Genomics 11(Suppl. 1):S1.
23. Elkin SK, Matthews AG, Oettinger MA. 2003. The C-terminal portion of RAG2 protects against transposition in vitro. EMBO J. 22:1931-38. (Pubitemid 36460149)
24. Sekiguchi JA, Whitlow S, Alt FW. 2001. Increased accumulation of hybridV(D)J joins in cells expressing truncated versus full-length RAGs. Mol. Cell 8:1383-90. (Pubitemid 34085007)
25. Tsai C-L, Schatz DG. 2003. Regulation of RAG1/RAG2-mediated transposition by GTP and the Cterminal region of RAG2. EMBO J. 22:1922-30. (Pubitemid 36460148)
26. Corneo B, WendlandRL, Deriano L, Cui X, Klein IA, et al. 2007. Ragmutations reveal robust alternative end joining. Nature 449:483-86. (Pubitemid 47509551)
27. Nemazee D. 2006. Receptor editing in lymphocyte development and central tolerance. Nat. Rev. Immunol. 6:728-40. (Pubitemid 44453459)
28. Jhunjhunwala S, van Zelm MC, Peak MM, Cutchin S, Riblet R, et al. 2008. The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell 133:265-79. (Pubitemid 351512300)
29. Difilippantonio S, Gapud E, Wong N, Huang C-Y, Mahowald G, et al. 2008. 53BP1 facilitates longrange DNA end-joining during V(D)J recombination. Nature 456:529-33. (Pubitemid 50304846)
30. Ramon-Maiques S, Kuo AJ, Carney D, Matthews AG, Oettinger MA, et al. 2007. The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2. Proc. Natl. Acad. Sci. USA 104:18993-98.
31. Liu Y, Subrahmanyam R, Chakraborty T, Sen R, Desiderio S. 2007. A plant homeodomain in RAG-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity 27:561-71. (Pubitemid 47615506)
32. Matthews AGW, Kuo AJ, Raḿon-Maiques S, Han S, Champagne KS, et al. 2007. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 450:1106-10. (Pubitemid 350273622)
33. Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG. 2010. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141:419-31.
34. Akamatsu Y, Monroe R, Dudley DD, Elkin SK, Gartner F, et al. 2003. Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice. Proc. Natl. Acad. Sci. USA 100:1209-14. (Pubitemid 36183981)
35. Dudley DD, Sekiguchi J, Zhu C, Sadofsky MJ, Whitlow S, et al. 2003. Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. J. Exp. Med. 198:1439-50. (Pubitemid 37392488)
36. Li Z, Dordai DI, Lee J, Desiderio S. 1996. A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Immunity 5:575-89. (Pubitemid 27062067)
37. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553-63.
38. Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, et al. 2007. Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv. Immunol. 94:157-214. (Pubitemid 46856611)
39. Odegard VH, Schatz DG. 2006. Targeting of somatic hypermutation. Nat. Rev. Immunol. 6:573-83. (Pubitemid 44134090)
40. Di Noia JM, Neuberger MS. 2007. Molecular mechanisms of antibody somatic hypermutation. Annu. Rev. Biochem. 76:1-22.
41. MacLennan ICM, Toellner K-M, Cunningham AF, Serre K, Sze DM-Y, et al. 2003. Extrafollicular antibody responses. Immunol. Rev. 194:8-18. (Pubitemid 36886424)
42. Dorsett Y, Robbiani DF, Jankovic M, Reina-San-Martin B, Eisenreich TR, Nussenzweig MC. 2007. A role for AID in chromosome translocations between c-myc and the IgH variable region. J. Exp. Med. 204:2225-32. (Pubitemid 47360881)
43. Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, et al. 2001. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 412:341-46. (Pubitemid 32691848)
44. Pan-Hammarstrom Q, Jones AM, Lahdesmaki A, Zhou W, Gatti RA, et al. 2005. Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells. J. Exp. Med. 201:189-94. (Pubitemid 40189427)
45. Yan CT, Boboila C, Souza EK, Franco S, Hickernell TR, et al. 2007. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 449:478-82. (Pubitemid 47509538)
46. Manis JP, Tian M, Alt FW. 2002. Mechanism and control of class-switch recombination. Trends Immunol. 23:31-39. (Pubitemid 34098959)
47. Janz S. 2006. Myc translocations in B cell and plasma cell neoplasms. DNA Repair 5:1213-24. (Pubitemid 44291611)
48. Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, et al. 2008. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451:841-45. (Pubitemid 351253166)
49. Chaudhuri J, Tian M, Khuong C, Chua K, Pinaud E, Alt FW. 2003. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422:726-30. (Pubitemid 36514112)
50. Yu K, Chedin F, Hsieh C-L, Wilson TE, Lieber MR. 2003. R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat. Immunol. 4:442-51. (Pubitemid 36592437)
51. Gomez-Gonzalez B, Aguilera A. 2007. Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex. Proc. Natl. Acad. Sci. USA 104:8409-14. (Pubitemid 47175501)
52. Lin C, Yang L, Tanasa B, Hutt K, Ju B-G, et al. 2009. Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Cell 139:1069-83.
53. Zarrin AA, Alt FW, Chaudhuri J, Stokes N, Kaushal D, et al. 2004. An evolutionarily conserved target motif for immunoglobulin class-switch recombination. Nat. Immunol. 5:1275-81. (Pubitemid 41057743)
54. Basu U, Chaudhuri J, Alpert C, Dutt S, Ranganath S, et al. 2005. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 438:508-11. (Pubitemid 41742023)
55. Dorsett Y, McBride KM, Jankovic M, Gazumyan A, Thai T-H, et al. 2008. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 28:630-38.
56. Teng G, Hakimpour P, Landgraf P, Rice A, Tuschl T, et al. 2008. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28:621-29.
57. Cheng HL, Vuong BQ, Basu U, Franklin A, Schwer B, et al. 2009. Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice. Proc. Natl. Acad. Sci. USA 106:2717-22.
58. McBride KM, Gazumyan A, Woo EM, Schwickert TA, Chait BT, Nussenzweig MC. 2008. Regulation of class switch recombination and somatic mutation by AID phosphorylation. J. Exp. Med. 205:2585-94.
59. Geisberger R, Rada C, Neuberger MS. 2009. The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence. Proc. Natl. Acad. Sci. USA 106:6736-41.
60. Okazaki I-m, Kotani A, Honjo T. 2007. Role of AID in tumorigenesis. Adv. Immunol. 94:245-73. (Pubitemid 46856613)
61. Robbiani DF, Bunting S, Feldhahn N, Bothmer A, Camps J, et al. 2009. AID produces DNA doublestrand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol. Cell 36:631-41.
62. Crouch EE, Li Z, Takizawa M, Fichtner-Feigl S, Gourzi P, et al. 2007. Regulation of AID expression in the immune response. J. Exp. Med. 204:1145-56. (Pubitemid 46798157)
63. Feldhahn N, Henke N, Melchior K, Duy C, Soh BN, et al. 2007. Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells. J. Exp.Med. 204:1157-66. (Pubitemid 46798158)
64. Mao C, Jiang L, Melo-Jorge M, Puthenveetil M, Zhang X, et al. 2004. T cell-independent somatic hypermutation in murine B cells with an immature phenotype. Immunity 20:133-44. (Pubitemid 38258390)
65. Sanz LA, Kota SK, Feil R. 2010. Genome-wide DNA demethylation in mammals. Genome Biol. 11:110.
66. Tycko B, Reynolds TC, Smith SD, Sklar J. 1989. Consistent breakage between consensus recombinase heptamers of chromosome 9 DNA in a recurrent chromosomal translocation of human T cell leukemia. J. Exp. Med. 169:369-77. (Pubitemid 19050637)
67. Taylor AM, Metcalfe JA, Thick J, Mak YF. 1996. Leukemia and lymphoma in ataxia telangiectasia. Blood 87:423-38. (Pubitemid 26030297)
68. Nambiar M, Kari V, Raghavan SC. 2008. Chromosomal translocations in cancer. Biochim. Biophys. Acta 1786:139-52.
69. Gladdy RA, Taylor MD, Williams CJ, Grandal I, Karaskova J, et al. 2003. The RAG-1/2 endonuclease causes genomic instability and controls CNS complications of lymphoblastic leukemia in p53/Prkdcdeficient mice. Cancer Cell 3:37-50. (Pubitemid 37448549)
70. Petiniot LK, Weaver Z, Vacchio M, Shen R, Wangsa D, et al. 2002. RAG-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Mol. Cell. Biol. 22:3174-77. (Pubitemid 34437475)
71. Marculescu R, Le T, Simon P, Jaeger U, Nadel B. 2002. V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. J. Exp. Med. 195:85-98. (Pubitemid 34074499)
72. Raghavan SC, Hsieh C-L, Lieber MR. 2005. Both V(D)J coding ends but neither signal end can recombine at the Bcl-2 major breakpoint region, and the rejoining is ligase IV dependent. Mol. Cell. Biol. 25:6475-84. (Pubitemid 41023223)
73. Raghavan SC, Swanson PC, Wu X, Hsieh C-L, Lieber MR. 2004. A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex. Nature 428:88-93. (Pubitemid 38332363)
74. Tsai AG, Lu H, Raghavan SC, Muschen M, Hsieh C-L, Lieber MR. 2008. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity. Cell 135:1130-42.
75. Boboila C, Jankovic M, YanCT, Wang JH, WesemannDR, et al. 2010. Alternative end-joining catalyzes robust IgH locus deletions and translocations in the combined absence of ligase 4 and Ku70. Proc. Natl. Acad. Sci. USA 107:3034-39.
76. Franco S, Gostissa M, Zha S, Lombard DB, Murphy MM, et al. 2006. H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Mol. Cell 21:201-14. (Pubitemid 43099936)
77. Ramiro AR, Jankovic M, Callen E, Difilippantonio S, Chen H-T, et al. 2006. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 440:105-9. (Pubitemid 43336276)
78. Ramiro AR, Jankovic M, Eisenreich T, Difilippantonio S, Chen-Kiang S, et al. 2004. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 118:431-38. (Pubitemid 39485663)
79. Wang JH, Gostissa M, YanCT, Goff P, Hickernell T, et al. 2009. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature 460:231-36.
80. Robbiani DF, Bothmer A, Callen E, Reina-San-Martin B, Dorsett Y, et al. 2008. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 135:1028-38.
81. Jankovic M, RobbianiDF, Dorsett Y, Eisenreich T, Xu Y, et al. 2010. Role of the translocation partner in protection against AID-dependent chromosomal translocations. Proc. Natl. Acad. Sci. USA 107:187-92.
82. Tsai AG, Engelhart AE, Hatmal MM, Houston SI, Hud NV, et al. 2009. Conformational variants of duplex DNA correlated with cytosine-rich chromosomal fragile sites. J. Biol. Chem. 284:7157-64.
83. Tsai AG, Lu Z, Lieber MR. 2010. The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas is a CpG-type translocation, but the t(11;18)(q21;q21)/API2-MALT1 translocation in MALT lymphomas is not. Blood 115:3640-41;author reply 1-2.
84. Wang JH, Alt FW, Gostissa M, Datta A, Murphy M, et al. 2008. Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. J. Exp. Med. 205:3079-90.
85. Marusawa H. 2008. Aberrant AID expression and human cancer development. Int. J. Biochem. Cell Biol. 40:1399-402.
86. Pauklin S, Serńandez IV, Bachmann G, Ramiro AR, Petersen-Mahrt SK. 2009. Estrogen directly activates AID transcription and function. J. Exp. Med. 206:99-111.
87. Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. 2008. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat. Rev. Cancer 8:11-23.
88. Mathas S, Kreher S, Meaburn KJ, J ̈ohrens K, Lamprecht B, et al. 2009. Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma. Proc. Natl. Acad. Sci. USA 106:5831-36.
89. Kha DT, Wang G, Natrajan N, Harrison L, Vasquez KM. 2010. Pathways for double-strand break repair in genetically unstable Z-DNA-forming sequences. J. Mol. Biol. 398:471-80.
90. Arlt MF, Durkin SG, Ragland RL, Glover TW. 2006. Common fragile sites as targets for chromosome rearrangements. DNA Repair 5:1126-35. (Pubitemid 44376448)
91. Sinclair P, Harrison CJ, Jarosov́a M, Foroni L. 2005. Analysis of balanced rearrangements of chromosome 6 in acute leukemia: clustered breakpoints in q22-q23 and possible involvement of c-MYB in a new recurrent translocation, t(6;7)(q23;q32 through 36). Haematologica 90:602-11. (Pubitemid 40780879)
92. Ferber MJ, Eilers P, Schuuring E, Fenton JAL, Fleuren GJ, et al. 2004. Positioning of cervical carcinoma and Burkitt lymphoma translocation breakpoints with respect to the human papillomavirus integration cluster in FRA8C at 8q24. Cancer Genet. Cytogenet. 154:1-9. (Pubitemid 39286165)
93. Felix CA, Kolaris CP, Osheroff N. 2006. Topoisomerase II and the etiology of chromosomal translocations. DNA Repair 5:1093-108. (Pubitemid 44291622)
94. Joannides M, Grimwade D. 2010. Molecular biology of therapy-related leukaemias. Clin. Transl. Oncol. 12:8-14.
95. Bassing CH, Alt FW. 2004. The cellular response to general and programmed DNA double strand breaks. DNA Repair 3:781-96. (Pubitemid 38997922)
96. Jeggo PA. 1998. Identification of genes involved in repair of DNA double-strand breaks in mammalian cells. Radiat. Res. 150:S80-91. (Pubitemid 28519053)
97. Yan CT, Kaushal D, Murphy M, Zhang Y, Datta A, et al. 2006. XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice. Proc. Natl. Acad. Sci. USA 103:7378-83. (Pubitemid 43727841)
98. Lavin MF. 2008. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat. Rev. Mol. Cell Biol. 9:759-69.
99. Boultwood J. 2001. Ataxia telangiectasia gene mutations in leukaemia and lymphoma. J. Clin. Pathol. 54:512-16. (Pubitemid 32642938)
100. Stucki M, Jackson SP. 2006. γH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair 5:534-43.
101. Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, et al. 2002. DNA damageinduced G2-M checkpoint activation by histone H2AX and 53BP1. Nat. Cell Biol. 4:993-97. (Pubitemid 35469431)
102. Nussenzweig A, Nussenzweig MC. 2010. Origin of chromosomal translocations in lymphoid cancer. Cell 141:27-38.
103. Bredemeyer AL, Sharma GG, Huang C-Y, Helmink BA, Walker LM, et al. 2006. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature 442:466-70. (Pubitemid 44264797)
104. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, et al. 2002. Genomic instability in mice lacking histone H2AX. Science 296:922-27. (Pubitemid 34464900)
105. Bassing CH, Suh H, Ferguson DO, Chua KF, Manis J, et al. 2003. Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors. Cell 114:359-70. (Pubitemid 36962934)
106. Zha S, Guo C, Boboila C, Oksenych V, Cheng H, et al. 2010. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature 469:250-54.
107. Reina-San-Martin B, Chen J, Nussenzweig A, Nussenzweig MC. 2007. Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1/ B cells. Eur. J. Immunol. 37:235-39. (Pubitemid 46128803)
108. Takeyama K, Monti S, Manis JP, Dal Cin P, Getz G, et al. 2008. Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas. Oncogene 27:318-22.
109. Barzilai A, Rotman G, Shiloh Y. 2002.ATMdeficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair 1:3-25. (Pubitemid 34475690)
110. Zha S, Sekiguchi J, Brush JW, Bassing CH, Alt FW. 2008. Complementary functions ofATMand H2AX in development and suppression of genomic instability. Proc. Natl. Acad. Sci. USA 105:9302-6.
111. Calĺen E, Jankovic M, Difilippantonio S, Daniel JA, Chen H-T, et al. 2007.ATMprevents the persistence and propagation of chromosome breaks in lymphocytes. Cell 130:63-75. (Pubitemid 47031324)
112. Liao MJ, Zhang XX, Hill R, Gao J, QumsiyehMB, et al. 1998. No requirement for V(D)J recombination in p53-deficient thymic lymphoma. Mol. Cell. Biol. 18:3495-501. (Pubitemid 28240521)
113. Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, et al. 2003. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114:371-83. (Pubitemid 36962935)
114. Morales JC, Franco S, Murphy MM, Bassing CH, Mills KD, et al. 2006. 53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis. Proc. Natl. Acad. Sci. USA 103:3310-15. (Pubitemid 43346466)
115. Ward IM, Difilippantonio S, Minn K, Mueller MD, Molina JR, et al. 2005. 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice. Mol. Cell. Biol. 25:10079-86. (Pubitemid 41572753)
116. Yannone SM, Khan IS, Zhou R-Z, Zhou T, Valerie K, Povirk LF. 2008. 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. 36:3354-65.
117. Moshous D, Callebaut I, de Chasseval R, Corneo B, Cavazzana-Calvo M, et al. 2001. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 105:177-86. (Pubitemid 32429508)
118. Riballo E, Doherty AJ, Dai Y, Stiff T, Oettinger MA, et al. 2001. Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. J. Biol. Chem. 276:31124-32.
119. Rucci F, Notarangelo LD, Fazeli A, Patrizi L, Hickernell T, et al. 2010. Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome. Proc. Natl. Acad. Sci. USA 107:3024-29.
120. Ahnesorg P, Smith P, Jackson SP. 2006. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124:301-13. (Pubitemid 43121979)
121. Buck D, Malivert L, de Chasseval R, Barraud A, Fondaǹeche M-C, et al. 2006. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 124:287-99. (Pubitemid 43121978)
122. Li G, Alt FW, Cheng H-L, Brush JW, Goff PH, et al. 2008. Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination. Mol. Cell 31:631-40.
123. Zha S, Alt FW, Cheng HL, Brush JW, Li G. 2007. Defective DNA repair and increased genomic instability in Cernunnos-XLF-deficient murine ES cells. Proc. Natl. Acad. Sci. USA 104:4518-23. (Pubitemid 47186257)
124. Tsai CJ, Kim SA, Chu G. 2007. Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc. Natl. Acad. Sci. USA 104:7851-56. (Pubitemid 47185840)
125. Boboila C, Yan C, Wesemann DR, Jankovic M, Wang JH, et al. 2010. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J. Exp. Med. 207:417-27.
126. Han L, Yu K. 2008. Altered kinetics of nonhomologous end joining and class switch recombination in ligase IV-deficient B cells. J. Exp. Med. 205:2745-53.
127. Jolly CJ, Cook AJ, Manis JP. 2008. Fixing DNA breaks during class switch recombination. J. Exp. Med. 205:509-13. (Pubitemid 351439298)
128. Franco S, MurphyMM, Li G, Borjeson T, Boboila C, Alt FW. 2008. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J. Exp.Med. 205:557-64. (Pubitemid 351439303)
129. Kabotyanski EB, Gomelsky L, Han JO, Stamato TD, Roth DB. 1998. Double-strand break repair in Ku86-and XRCC4-deficient cells. Nucleic Acids Res. 26:5333-42. (Pubitemid 28542732)
130. Liang F, Jasin M. 1996. Ku80-deficient cells exhibit excess degradation of extrachromosomal DNA. J. Biol. Chem. 271:14405-11. (Pubitemid 26190339)
131. Verkaik NS, Esveldt-van Lange REE, van Heemst D, Br̈uggenwirth HT, Hoeijmakers JHJ, et al. 2002. Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells. Eur. J. Immunol. 32:701-9. (Pubitemid 34257548)
132. Wang H, Zeng ZC, Perrault AR, Cheng X, Qin W, Iliakis G. 2001. Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells. Nucleic Acids Res. 29:1653-60. (Pubitemid 32427845)
133. Wang H, Perrault AR, Takeda Y, Qin W, Wang H, Iliakis G. 2003. Biochemical evidence for Kuindependent backup pathways of NHEJ. Nucleic Acids Res. 31:5377-88. (Pubitemid 37441906)
134. Guirouilh-Barbat J, Huck S, Bertrand P, Pirzio L, Desmaze C, et al. 2004. Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells. Mol. Cell 14:611-23. (Pubitemid 38744575)
135. Guirouilh-Barbat J, Rass E, Plo I, Bertrand P, Lopez BS. 2007. Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends. Proc. Natl. Acad. Sci. 104:20902-7.
136. Nevaldine B, Longo JA, Hahn PJ. 1997. The scid defect results in much slower repair of DNA doublestrand breaks but not high levels of residual breaks. Radiat. Res. 147:535-40. (Pubitemid 27204089)
137. Chen S, Inamdar KV, Pfeiffer P, Feldmann E, Hannah MF, et al. 2001. Accurate in vitro end joining of a DNA double strand break with partially cohesive 3-overhangs and 3-phosphoglycolate termini: effect of Ku on repair fidelity. J. Biol. Chem. 276:24323-30.
138. Feldmann E, Schmiemann V, Goedecke W, Reichenberger S, Pfeiffer P. 2000. DNA double-strand break repair in cell-free extracts from Ku80-deficient cells: implications for Ku serving as an alignment factor in non-homologous DNA end joining. Nucleic Acids Res. 28:2585-96. (Pubitemid 30420858)
139. Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, et al. 2000. The nonhomologous end-joining pathway ofDNA repair is required for genomic stability and the suppression of translocations. Proc. Natl. Acad. Sci. USA 97:6630-33. (Pubitemid 30412765)
140. Gostissa M, Yan CT, Bianco JM, Cogńe M, Pinaud E, Alt FW. 2009. Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3- regulatory region. Nature 462:803-7.
141. Rooney S, Sekiguchi J, Whitlow S, Eckersdorff M, Manis JP, et al. 2004. Artemis and p53 cooperate to suppress oncogenic N-myc amplification in progenitor B cells. Proc. Natl. Acad. Sci. USA 101:2410-15. (Pubitemid 38269325)
142. Lee Y, McKinnon PJ. 2002.DNAligase IV suppressesmedulloblastoma formation. Cancer Res. 62:6395-99.
143. Weinstock DM, Elliott B, Jasin M. 2006. A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair. Blood 107:777-80. (Pubitemid 43076405)
144. Zhang Y, Rowley JD. 2006. Chromatin structural elements and chromosomal translocations in leukemia. DNA Repair 5:1282-97. (Pubitemid 44291613)
145. Meaburn KJ, Misteli T, Soutoglou E. 2007. Spatial genome organization in the formation of chromosomal translocations. Semin. Cancer Biol. 17:80-90. (Pubitemid 46054486)
146. Cremer T, Cremer C. 2001. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2:292-301. (Pubitemid 33674777)
147. Parada LA, McQueen PG, Misteli T. 2004. Tissue-specific spatial organization of genomes. Genome Biol. 5:R44.
148. Dekker J. 2008. Gene regulation in the third dimension. Science 319:1793-94. (Pubitemid 351451557)
149. Schneider R, Grosschedl R. 2007. Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev. 21:3027-43. (Pubitemid 350223521)
150. Roix JJ, McQueen PG, Munson PJ, Parada LA, Misteli T. 2003. Spatial proximity of translocation-prone gene loci in human lymphomas. Nat. Genet. 34:287-91. (Pubitemid 36792860)
151. Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, et al. 2007. Myc dynamically and preferentially relocates to a transcription factory occupied by Igh. PLoS Biol. 5:e192.
152. Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE. 2000. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 290:138-41.
153. Degner SC, Wong TP, Jankevicius G, Feeney AJ. 2009. Cutting edge: developmental stage-specific recruitment of cohesin toCTCFsites throughout immunoglobulin loci during B lymphocyte development. J. Immunol. 182:44-48.
154. Hadjur S, Williams LM, Ryan NK, Cobb BS, Sexton T, et al. 2009. Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature 460:410-13.
155. Hou C, Dale R, Dean A. 2010. Cell type specificity of chromatin organization mediated by CTCF and cohesin. Proc. Natl. Acad. Sci. USA 107:3651-56.
156. Wuerffel R, Wang L, Grigera F, Manis J, Selsing E, et al. 2007. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase. Immunity 27:711-22. (Pubitemid 350110545)
157. Bothmer A, Robbiani DF, Feldhahn N, Gazumyan A, Nussenzweig A,
158. Lisby M, Antunez de Mayolo A, Mortensen UH, Rothstein R. 2003. Cell cycle-regulated centers of DNA double-strand break repair. Cell Cycle 2:479-83.
159. Nagai S, Dubrana K, Tsai-Pflugfelder M, DavidsonMB, Roberts TM, et al. 2008. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322:597-602.
160. Oza P, Jaspersen SL, Miele A, Dekker J, Peterson CL. 2009. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 23:912-27.
161. Kruhlak MJ, Celeste A, Dellaire G, Fernandez-Capetillo O, MullerWG, et al. 2006. Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks. J. Cell Biol. 172:823-34.
162. Nelms BE, Maser RS, MacKay JF, Lagally MG, Petrini JH. 1998. In situ visualization of DNA doublestrand break repair in human fibroblasts. Science 280:590-92. (Pubitemid 28227762)
163. Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, et al. 2004. Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science 303:92-95. (Pubitemid 38055778)
164. Soutoglou E, Dorn JF, Sengupta K, Jasin M, Nussenzweig A, et al. 2007. Positional stability of single double-strand breaks in mammalian cells. Nat. Cell Biol. 9:675-82. (Pubitemid 47214730)
165. Dimitrova N, Chen Y-CM, Spector DL, de Lange T. 2008. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature 456:524-28. (Pubitemid 50304845)
166. Henderson A, Calame K. 1998. Transcriptional regulation during B cell development. Annu. Rev. Immunol. 16:163-200. (Pubitemid 28183363)
167. Khamlichi AA, Pinaud E, Decourt C, Chauveau C, Cogńe M. 2000. The 3- IgH regulatory region: a complex structure in a search for a function. Adv. Immunol. 75:317-45.
168. Truffinet V, Pinaud E, Cogńe N, Petit B, Guglielmi L, et al. 2007. The 3- IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype. J. Immunol. 179:6033-42.
169. Wang J, Boxer LM. 2005. Regulatory elements in the immunoglobulin heavy chain gene 3-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells. J. Biol. Chem. 280:12766-73.
170. Yan Y, Park SS, Janz S, Eckhardt LA. 2007. In a model of immunoglobulin heavy-chain (IGH)/MYC translocation, the Igh 3- regulatory region induces MYC expression at the immature stage of B cell development. Genes Chromosomes Cancer 46:950-59.
171. Pasqualucci L, Bereschenko O, Niu H, Klein U, Basso K, et al. 2003. Molecular pathogenesis of non-Hodgkin's lymphoma: the role of Bcl-6. Leuk. Lymphoma 44(Suppl. 3):S5-12.
172. Zha S, Bassing CH, Sanda T, Brush JW, Patel H, et al. 2010. ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. J. Exp. Med. 207:1369-80.
173. Avet-Loiseau H, Gerson F, Magrangeas F, Minvielle S, Harousseau JL, et al. 2001. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood 98:3082-86.
174. Shou Y, Martelli ML, Gabrea A, Qi Y, Brents LA, et al. 2000. Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. Proc. Natl. Acad. Sci. USA 97:228-33. (Pubitemid 30055813)
175. Mart́in-Subero JI, Odero MD, Hernandez R, Cigudosa JC, Agirre X, et al. 2005 Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas. Genes Chromosomes Cancer 43, 414-23.
176. Druker BJ. 2008. Translation of the Philadelphia chromosome into therapy for CML. Blood 112:4808-17