Activation-induced cytidine deaminase-initiated off-target DNA breaks are detected and resolved during S phase

Journal of Immunology

Volumn 189, Issue 5, 2012, Pages 2374-2382

  Hasham, Muneer G ^a   Snow, Kathy J ^a   Donghia, Nina M ^a   Branca, Jane A ^a   Lessard, Mark D ^a   Stavnezer, Janet ^b   Shopland, Lindsay S ^a   Mills, Kevin D ^a  

^a JACKSON LABORATORY   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; IMMUNOGLOBULIN;

ANIMAL CELL; ARTICLE; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CONTROLLED STUDY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ENZYME ACTIVITY; G1 PHASE CELL CYCLE CHECKPOINT; GENE; GENE REARRANGEMENT; GENETIC RECOMBINATION; IGH GENE; MOUSE; NONHUMAN; OFF TARGET DOUBLE STRANDED DNA BREAK; PRIORITY JOURNAL;

ANIMALS; B-LYMPHOCYTES; CELLS, CULTURED; CYTIDINE DEAMINASE; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; G1 PHASE; IMMUNOGLOBULIN CLASS SWITCHING; IMMUNOGLOBULIN ISOTYPES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; S PHASE;

EID: 84865419410     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1200414     Document Type: Article

References (51)

1. Chaudhuri, J., and F. W. Alt. 2004. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol. 4: 541-552.
2. Chaudhuri, J., U. Basu, A. Zarrin, C. Yan, S. Franco, T. Perlot, B. Vuong, J. Wang, R. T. Phan, A. Datta, et al. 2007. Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv. Immunol. 94: 157-214.
3. Stavnezer, J., J. E. Guikema, and C. E. Schrader. 2008. Mechanism and regulation of class switch recombination. Annu. Rev. Immunol. 26: 261-292.
4. Stavnezer, J., and C. T. Amemiya. 2004. Evolution of isotype switching. Semin. Immunol. 16: 257-275.
5. Stavnezer, J. 2011. Complex regulation and function of activation-induced cytidine deaminase. Trends Immunol. 32: 194-201.
6. Pavri, R., and M. C. Nussenzweig. 2011. AID targeting in antibody diversity. Adv. Immunol. 110: 1-26.
7. Nussenzweig, M. C., and F.W. Alt. 2004. Antibody diversity: one enzyme to rule them all. Nat. Med. 10: 1304-1305.
8. Ramiro, A. R., and M. C. Nussenzweig. 2004. Immunology: aid for AID. Nature 430: 980-981.
9. Chua, K. F., F. W. Alt, and J. P. Manis. 2002. The function of AID in somatic mutation and class switch recombination: upstream or downstream of DNA breaks. J. Exp. Med. 195: F37-F41.
10. Storb, U., and J. Stavnezer. 2002. Immunoglobulin genes: generating diversity with AID and UNG. Curr. Biol. 12: R725-R727.
11. Muramatsu, M., K. Kinoshita, S. Fagarasan, S. Yamada, Y. Shinkai, and T. Honjo. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553-563.
12. Chaudhuri, J., M. Tian, C. Khuong, K. Chua, E. Pinaud, and F. W. Alt. 2003. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422: 726-730.
13. Boboila, C., C. Yan, D. R. Wesemann, M. Jankovic, J. H. Wang, J. P. Manis, A. Nussenzweig, M. Nussenzweig, and F. W. Alt. 2010. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J. Exp. Med. 207: 417-427.
14. Boboila, C., M. Jankovic, C. T. Yan, J. H. Wang, D. R. Wesemann, T. Zhang, A. Fazeli, L. Feldman, A. Nussenzweig, M. Nussenzweig, and F. W. Alt. 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: 3034-3039.
15. Schrader, C. E., J. E. Guikema, E. K. Linehan, E. Selsing, and J. Stavnezer. 2007. Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair. J. Immunol. 179: 6064-6071.
16. Franco, S., M. M. Murphy, G. Li, T. Borjeson, C. Boboila, and F. W. Alt. 2008. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J. Exp. Med. 205: 557-564.
17. Yan, C. T., C. Boboila, E. K. Souza, S. Franco, T. R. Hickernell, M. Murphy, S. Gumaste, M. Geyer, A. A. Zarrin, J. P. Manis, et al. 2007. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 449: 478-482.
18. Rooney, S., J. Chaudhuri, and F. W. Alt. 2004. The role of the non-homologous end-joining pathway in lymphocyte development. Immunol. Rev. 200: 115-131.
19. O'Driscoll, M., K. M. Cerosaletti, P. M. Girard, Y. Dai, M. Stumm, B. Kysela, B. Hirsch, A. Gennery, S. E. Palmer, J. Seidel, et al. 2001. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol. Cell 8: 1175-1185.
20. Rush, J. S., M. Liu, V. H. Odegard, S. Unniraman, and D. G. Schatz. 2005. Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination. Proc. Natl. Acad. Sci. USA 102: 13242-13247.
21. Hodgkin, P. D., J. H. Lee, and A. B. Lyons. 1996. B cell differentiation and isotype switching is related to division cycle number. J. Exp. Med. 184: 277-281.
22. Liu, M., and D. G. Schatz. 2009. Balancing AID and DNA repair during somatic hypermutation. Trends Immunol. 30: 173-181.
23. Liu, M., J. L. Duke, D. J. Richter, C. G. Vinuesa, C. C. Goodnow, S. H. Kleinstein, and D. G. Schatz. 2008. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451: 841-845.
24. Staszewski, O., R. E. Baker, A. J. Ucher, R. Martier, J. Stavnezer, and J. E. Guikema. 2011. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells. Mol. Cell 41: 232-242.
25. Hasham, M. G., N. M. Donghia, E. Coffey, J. Maynard, K. J. Snow, J. Ames, R. Y. Wilpan, Y. He, B. L. King, and K. D. Mills. 2010. Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nat. Immunol. 11: 820-826.
26. Robbiani, D. F., A. Bothmer, E. Callen, B. Reina-San-Martin, Y. Dorsett, S. Difilippantonio, D. J. Bolland, H. T. Chen, A. E. Corcoran, A. Nussenzweig, and M. C. Nussenzweig. 2008. AID is required for the chromosomal breaks in cmyc that lead to c-myc/IgH translocations. Cell 135: 1028-1038.
27. Shen, H. M. 2007. Activation-induced cytidine deaminase acts on double-strand breaks in vitro. Mol. Immunol. 44: 974-983.
28. Moynahan, M. E., and M. Jasin. 2010. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat. Rev. Mol. Cell Biol. 11: 196-207.
29. Hartlerode, A. J., and R. Scully. 2009. Mechanisms of double-strand break repair in somatic mammalian cells. Biochem. J. 423: 157-168.
30. Gostissa, M., F. W. Alt, and R. Chiarle. 2011. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annu. Rev. Immunol. 29: 319-350.
31. Pasqualucci, L., G. Bhagat, M. Jankovic, M. Compagno, P. Smith, M. Muramatsu, T. Honjo, H. C. Morse, III, M. C. Nussenzweig, and R. Dalla-Favera. 2008. AID is required for germinal center-derived lymphomagenesis. Nat. Genet. 40: 108-112.
32. Ramiro, A. R., M. Jankovic, E. Callen, S. Difilippantonio, H. T. Chen, K. M. McBride, T. R. Eisenreich, J. Chen, R. A. Dickins, S. W. Lowe, et al. 2006. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 440: 105-109.
33. Donehower, L. A., M. Harvey, B. L. Slagle, M. J. McArthur, C. A. Montgomery, Jr., J. S. Butel, and A. Bradley. 1992. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215-221.
34. Caddle, L. B., M. G. Hasham, W. H. Schott, B. J. Shirley, and K. D. Mills. 2008. Homologous recombination is necessary for normal lymphocyte development. Mol. Cell. Biol. 28: 2295-2303.
35. Dudley, D. D., J. P. Manis, A. A. Zarrin, L. Kaylor, M. Tian, and F. W. Alt. 2002. Internal IgH class switch region deletions are position-independent and enhanced by AID expression. Proc. Natl. Acad. Sci. USA 99: 9984-9989.
36. Orii, K. E., Y. Lee, N. Kondo, and P. J. McKinnon. 2006. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc. Natl. Acad. Sci. USA 103: 10017-10022.
37. Yamane, A., W. Resch, N. Kuo, S. Kuchen, Z. Li, H. W. Sun, D. F. Robbiani, K. McBride, M. C. Nussenzweig, and R. Casellas. 2011. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat. Immunol. 12: 62-69.
38. Petersen, S., R. Casellas, B. Reina-San-Martin, H. T. Chen, M. J. Difilippantonio, P. C. Wilson, L. Hanitsch, A. Celeste, M. Muramatsu, D. R. Pilch, et al. 2001. AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature 414: 660-665.
39. Rogakou, E. P., D. R. Pilch, A. H. Orr, V. S. Ivanova, and W. M. Bonner. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273: 5858-5868.
40. Guikema, J. E., C. E. Schrader, M. H. Brodsky, E. K. Linehan, A. Richards, N. El Falaky, D. H. Li, H. K. Sluss, E. Szomolanyi-Tsuda, and J. Stavnezer. 2010. p53 represses class switch recombination to IgG2a through its antioxidant function. J. Immunol. 184: 6177-6187.
41. Phan, R. T., and R. Dalla-Favera. 2004. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 432: 635-639.
42. Shansab, M., and E. Selsing. 2011. p21 is dispensable for AID-mediated class switch recombination and mutagenesis of immunoglobulin genes during somatic hypermutation. Mol. Immunol. 48: 973-978.
43. Sherman, M. H., A. I. Kuraishy, C. Deshpande, J. S. Hong, N. A. Cacalano, R. A. Gatti, J. P. Manis, M. A. Damore, M. Pellegrini, and M. A. Teitell. 2010. AID-induced genotoxic stress promotes B cell differentiation in the germinal center via ATM and LKB1 signaling. Mol. Cell 39: 873-885.
44. Starczynski, J., W. Simmons, J. R. Flavell, P. J. Byrd, G. S. Stewart, H. S. Kullar, A. Groom, J. Crocker, P. A. Moss, G. M. Reynolds, et al. 2003. Variations in ATM protein expression during normal lymphoid differentiation and among B-cell- derived neoplasias. Am. J. Pathol. 163: 423-432.
45. Robbiani, D. F., S. Bunting, N. Feldhahn, A. Bothmer, J. Camps, S. Deroubaix, K. M. McBride, I. A. Klein, G. Stone, T. R. Eisenreich, et al. 2009. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol. Cell 36: 631-641.
46. Sale, J. E., D. M. Calandrini, M. Takata, S. Takeda, and M. S. Neuberger. 2001. Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation. Nature 412: 921-926.
47. Pan, Q., C. Petit-Frére, A. Lähdesmäki, H. Gregorek, K. H. Chrzanowska, and L. Hammarström. 2002. Alternative end joining during switch recombination in patients with ataxia-telangiectasia. Eur. J. Immunol. 32: 1300-1308.
48. Dudley, D. D., J. Chaudhuri, C. H. Bassing, and F. W. Alt. 2005. Mechanism and control of V(D)J recombination versus class switch recombination: similarities and differences. Adv. Immunol. 86: 43-112.
49. Bothmer, A., D. F. Robbiani, N. Feldhahn, A. Gazumyan, A. Nussenzweig, and M. C. Nussenzweig. 2010. 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination. J. Exp. Med. 207: 855-865.
50. -/- B cells. Eur. J. Immunol. 37: 235-239.
51. Lumsden, J. M., T. McCarty, L. K. Petiniot, R. Shen, C. Barlow, T. A. Wynn, H. C. Morse, III, P. J. Gearhart, A. Wynshaw-Boris, E. E. Max, and R. J. Hodes. 2004. Immunoglobulin class switch recombination is impaired in Atm-deficient mice. J. Exp. Med. 200: 1111-1121.