Role of Activation-Induced Cytidine Deaminase in Inflammation-Associated Cancer Development

Advances in Immunology

Volumn 111, Issue , 2011, Pages 109-141

  Marusawa, Hiroyuki ^a   Takai, Atsushi ^a   Chiba, Tsutomu ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

AID; Cancer; Inflammation; Mutation

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; ADENINE; CYTOKINE; CYTOSINE; GUANINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NUCLEOTIDE; THYMINE;

ANTIBODY PRODUCTION; B LYMPHOCYTE; BILE DUCT CARCINOMA; BOOK; CANCER GENETICS; CARCINOGENESIS; COLON MUCOSA; COLORECTAL CANCER; DISEASE ASSOCIATION; DISEASE COURSE; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME REGULATION; ENZYME SUBSTRATE; EPITHELIUM CELL; GASTRITIS; GENE MUTATION; GENE SWITCHING; GENETIC DISORDER; GENETIC RECOMBINATION; GENETIC SUSCEPTIBILITY; HELICOBACTER INFECTION; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOGLOBULIN GENE; IMMUNOPATHOGENESIS; IMMUNOSTIMULATION; IN VIVO STUDY; INFLAMMATION; LIVER CELL; LIVER CELL CARCINOMA; LYMPHOID CELL; MALIGNANT NEOPLASTIC DISEASE; MUTAGENESIS; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; SOMATIC HYPERMUTATION; STOMACH CANCER; STOMACH EPITHELIUM; T LYMPHOCYTE; TRANSCRIPTION REGULATION;

EID: 80053451874     PISSN: 00652776     EISSN: 15578445     Source Type: Book Series    
DOI: 10.1016/B978-0-12-385991-4.00003-9     Document Type: Chapter

References (172)

1. Aoufouchi S., Faili A., Zober C., D'Orlando O., Weller S., Weill J.C., Reynaud C.A. Proteasomal degradation restricts the nuclear lifespan of AID. J. Exp. Med. 2008, 205:1357-1368.
2. Bachl J., Carlson C., Gray-Schopfer V., Dessing M., Olsson C. Increased transcription levels induce higher mutation rates in a hypermutating cell line. J. Immunol. 2001, 166:5051-5057.
3. Barreto V.M., Ramiro A.R., Nussenzweig M.C. Activation-induced deaminase: Controversies and open questions. Trends Immunol. 2005, 26:90-96.
4. Basu U., Chaudhuri J., Alpert C., Dutt S., Ranganath S., Li G., Schrum J.P., Manis J.P., Alt F.W. The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 2005, 438:508-511.
5. Basu U., Chaudhuri J., Phan R.T., Datta A., Alt F.W. Regulation of activation induced deaminase via phosphorylation. Adv. Exp. Med. Biol. 2007, 596:129-137.
6. Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J., Zhang T., Myers D., Wasserman C.R., Wesemann D.R., Januszyk K., Gregory R.I., et al. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 2011, 144:353-363.
7. Both G.W., Taylor L., Pollard J.W., Steele E.J. Distribution of mutations around rearranged heavy-chain antibody variable-region genes. Mol. Cell. Biol. 1990, 10:5187-5196.
8. Bransteitter R., Pham P., Calabrese P., Goodman M.F. Biochemical analysis of hypermutational targeting by wild type and mutant activation-induced cytidine deaminase. J. Biol. Chem. 2004, 279:51612-51621.
9. Brar S.S., Watson M., Diaz M. Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks. J. Biol. Chem. 2004, 279:26395-26401.
10. 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.
11. Chaudhuri J., Alt F.W. Class-switch recombination: Interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol. 2004, 4:541-552.
12. Chaudhuri J., Tian M., Khuong C., Chua K., Pinaud E., Alt F.W. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 2003, 422:726-730.
13. Chaudhuri J., Khuong C., Alt F.W. Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 2004, 430:992-998.
14. Chen S.H., Habib G., Yang C.Y., Gu Z.W., Lee B.R., Weng S.A., Silberman S.R., Cai S.J., Deslypere J.P., Rosseneu M., et al. Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 1987, 238:363-366.
15. Cheng H.L., Vuong B.Q., Basu U., Franklin A., Schwer B., Astarita J., Phan R.T., Datta A., Manis J., Alt F.W., Chaudhuri J. Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice. Proc. Natl. Acad. Sci. USA 2009, 106:2717-2722.
16. Chiba T., Seno H., Marusawa H., Wakatsuki Y., Okazaki K. Host factors are important in determining clinical outcomes of Helicobacter pylori infection. J. Gastroenterol. 2006, 41:1-9.
17. Christmann M., Tomicic M.T., Roos W.P., Kaina B. Mechanisms of human DNA repair: An update. Toxicology 2003, 193:3-34.
18. Cleary S.P., Cotterchio M., Jenkins M.A., Kim H., Bristow R., Green R., Haile R., Hopper J.L., LeMarchand L., Lindor N., Parfrey P., Potter J., et al. Germline MutY human homologue mutations and colorectal cancer: A multisite case-control study. Gastroenterology 2009, 136:1251-1260.
19. Conticello S.G. The AID/APOBEC family of nucleic acid mutators. Genome Biol. 2008, 9:229.
20. Conticello S.G., Ganesh K., Xue K., Lu M., Rada C., Neuberger M.S. Interaction between antibody-diversification enzyme AID and spliceosome-associated factor CTNNBL1. Mol. Cell 2008, 31:474-484.
21. Cory S., Jackson J., Adams J.M. Deletions in the constant region locus can account for switches in immunoglobulin heavy chain expression. Nature 1980, 285:450-456.
22. Davis M.M., Calame K., Early P.W., Livant D.L., Joho R., Weissman I.L., Hood L. An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature 1980, 283:733-739.
23. Davis M.M., Kim S.K., Hood L.E. DNA sequences mediating class switching in alpha-immunoglobulins. Science 1980, 209:1360-1365.
24. de Yebenes V.G., Ramiro A.R. Activation-induced deaminase: Light and dark sides. Trends Mol. Med. 2006, 12:432-439.
25. de Yebenes V.G., Belver L., Pisano D.G., Gonzalez S., Villasante A., Croce C., He L., Ramiro A.R. miR-181b negatively regulates activation-induced cytidine deaminase in B cells. J. Exp. Med. 2008, 205:2199-2206.
26. Delker R.K., Fugmann S.D., Papavasiliou F.N. A coming-of-age story: Activation-induced cytidine deaminase turns 10. Nat. Immunol. 2009, 10:1147-1153.
27. Deutsch A.J., Aigelsreiter A., Staber P.B., Beham A., Linkesch W., Guelly C., Brezinschek R.I., Fruhwirth M., Emberger W., Buettner M., Beham-Schmid C., Neumeister P. MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation. Blood 2007, 109:3500-3504.
28. Dickerson S.K., Market E., Besmer E., Papavasiliou F.N. AID mediates hypermutation by deaminating single stranded DNA. J. Exp. Med. 2003, 197:1291-1296.
29. Dorsett Y., Robbiani D.F., Jankovic M., Reina-San-Martin B., Eisenreich T.R., Nussenzweig M.C. A role for AID in chromosome translocations between c-myc and the IgH variable region. J. Exp. Med. 2007, 204:2225-2232.
30. Dorsett Y., McBride K.M., Jankovic M., Gazumyan A., Thai T.H., Robbiani D.F., Di Virgilio M., Reina San-Martin B., Heidkamp G., Schwickert T.A., Eisenreich T., Rajewsky K., et al. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 2008, 28:630-638.
31. Dunnick W., Hertz G.Z., Scappino L., Gritzmacher C. DNA sequences at immunoglobulin switch region recombination sites. Nucleic Acids Res. 1993, 21:365-372.
32. Durandy A., Revy P., Imai K., Fischer A. Hyper-immunoglobulin M syndromes caused by intrinsic B-lymphocyte defects. Immunol. Rev. 2005, 203:67-79.
33. Endo Y., Marusawa H., Kinoshita K., Morisawa T., Sakurai T., Okazaki I.M., Watashi K., Shimotohno K., Honjo T., Chiba T. Expression of activation-induced cytidine deaminase in human hepatocytes via NF-kappaB signaling. Oncogene 2007, 26:5587-5595.
34. Endo Y., Marusawa H., Kou T., Nakase H., Fujii S., Fujimori T., Kinoshita K., Honjo T., Chiba T. Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. Gastroenterology 2008, 135:889-898. 898.e1-3.
35. Erdman S.E., Poutahidis T. Roles for inflammation and regulatory T cells in colon cancer. Toxicol. Pathol. 2010, 38:76-87.
36. Faili A., Aoufouchi S., Flatter E., Gueranger Q., Reynaud C.A., Weill J.C. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature 2002, 419:944-947.
37. Feldhahn N., Henke N., Melchior K., Duy C., Soh B.N., Klein F., von Levetzow G., Giebel B., Li A., Hofmann W.K., Jumaa H., Muschen M. Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells. J. Exp. Med. 2007, 204:1157-1166.
38. Fukita Y., Jacobs H., Rajewsky K. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 1998, 9:105-114.
39. Fukuhara N., Nakamura T., Nakagawa M., Tagawa H., Takeuchi I., Yatabe Y., Morishima Y., Nakamura S., Seto M. Chromosomal imbalances are associated with outcome of Helicobacter pylori eradication in t(11;18)(q21;q21) negative gastric mucosa-associated lymphoid tissue lymphomas. Genes Chromosomes Cancer 2007, 46:784-790.
40. Geisberger R., Rada C., Neuberger M.S. 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 2009, 106:6736-6741.
41. Goff S.P. Death by deamination: A novel host restriction system for HIV-1. Cell 2003, 114:281-283.
42. Golding G.B., Gearhart P.J., Glickman B.W. Patterns of somatic mutations in immunoglobulin variable genes. Genetics 1987, 115:169-176.
43. Gonda H., Sugai M., Nambu Y., Katakai T., Agata Y., Mori K.J., Yokota Y., Shimizu A. The balance between Pax5 and Id2 activities is the key to AID gene expression. J. Exp. Med. 2003, 198:1427-1437.
44. Gonzalez-Amaro R., Garcia-Monzon C., Garcia-Buey L., Moreno-Otero R., Alonso J.L., Yague E., Pivel J.P., Lopez-Cabrera M., Fernandez-Ruiz E., Sanchez-Madrid F. Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis. J. Exp. Med. 1994, 179:841-848.
45. Gourzi P., Leonova T., Papavasiliou F.N. Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-kappaB. J. Exp. Med. 2007, 204:259-265.
46. Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., et al. Patterns of somatic mutation in human cancer genomes. Nature 2007, 446:153-158.
47. Greeve J., Philipsen A., Krause K., Klapper W., Heidorn K., Castle B.E., Janda J., Marcu K.B., Parwaresch R. Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas. Blood 2003, 101:3574-3580.
48. Greten F.R., Eckmann L., Greten T.F., Park J.M., Li Z.W., Egan L.J., Kagnoff M.F., Karin M. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118:285-296.
49. Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R., Stavnezer J., Schrader C.E. APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. J. Exp. Med. 2007, 204:3017-3026.
50. Hahn W.C., Weinberg R.A. Rules for making human tumor cells. N. Engl. J. Med. 2002, 347:1593-1603.
51. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000, 100:57-70.
52. Harris R.S., Liddament M.T. Retroviral restriction by APOBEC proteins. Nat. Rev. Immunol. 2004, 4:868-877.
53. Heintel D., Kroemer E., Kienle D., Schwarzinger I., Gleiss A., Schwarzmeier J., Marculescu R., Le T., Mannhalter C., Gaiger A., Stilgenbauer S., Dohner H., et al. High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia. Leukemia 2004, 18:756-762.
54. Hoeijmakers J.H. Genome maintenance mechanisms for preventing cancer. Nature 2001, 411:366-374.
55. Honjo T., Kataoka T. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc. Natl. Acad. Sci. USA 1978, 75:2140-2144.
56. Honjo T., Kinoshita K., Muramatsu M. Molecular mechanism of class switch recombination: Linkage with somatic hypermutation. Annu. Rev. Immunol. 2002, 20:165-196.
57. Iacobucci I., Lonetti A., Messa F., Ferrari A., Cilloni D., Soverini S., Paoloni F., Arruga F., Ottaviani E., Chiaretti S., Messina M., Vignetti M., et al. Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR-ABL1-positive acute lymphoblastic leukemia patients. Leukemia 2010, 24:66-73.
58. Ikeda K., Marusawa H., Osaki Y., Nakamura T., Kitajima N., Yamashita Y., Kudo M., Sato T., Chiba T. Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: A prospective study. Ann. Intern. Med. 2007, 146:649-656.
59. Ito S., Nagaoka H., Shinkura R., Begum N., Muramatsu M., Nakata M., Honjo T. Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1. Proc. Natl. Acad. Sci. USA 2004, 101:1975-1980.
60. Iwasato T., Shimizu A., Honjo T., Yamagishi H. Circular DNA is excised by immunoglobulin class switch recombination. Cell 1990, 62:143-149.
61. Karin M., Greten F.R. NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 2005, 5:749-759.
62. Kasama Y., Sekiguchi S., Saito M., Tanaka K., Satoh M., Kuwahara K., Sakaguchi N., Takeya M., Hiasa Y., Kohara M., Tsukiyama-Kohara K. Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo. Blood 2010, 116:4926-4933.
63. Kataoka T., Kawakami T., Takahashi N., Honjo T. Rearrangement of immunoglobulin gamma 1-chain gene and mechanism for heavy-chain class switch. Proc. Natl. Acad. Sci. USA 1980, 77:919-923.
64. KewalRamani V.N., Coffin J.M. Virology. Weapons of mutational destruction. Science 2003, 301:923-925.
65. Kinoshita K., Honjo T. Linking class-switch recombination with somatic hypermutation. Nat. Rev. Mol. Cell Biol. 2001, 2:493-503.
66. Kinoshita K., Nonaka T. The dark side of activation-induced cytidine deaminase: Relationship with leukemia and beyond. Int. J. Hematol. 2006, 83:201-207.
67. Klemm L., Duy C., Iacobucci I., Kuchen S., von Levetzow G., Feldhahn N., Henke N., Li Z., Hoffmann T.K., Kim Y.M., Hofmann W.K., Jumaa H., et al. The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia. Cancer Cell 2009, 16:232-245.
68. Kobayashi M., Aida M., Nagaoka H., Begum N.A., Kitawaki Y., Nakata M., Stanlie A., Doi T., Kato L., Okazaki I.M., Shinkura R., Muramatsu M., et al. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination. Proc. Natl. Acad. Sci. USA 2009, 106:22375-22380.
69. Komeno Y., Kitaura J., Watanabe-Okochi N., Kato N., Oki T., Nakahara F., Harada Y., Harada H., Shinkura R., Nagaoka H., Hayashi Y., Honjo T., et al. AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. Leukemia 2010, 24:1018-1024.
70. Komori J., Marusawa H., Machimoto T., Endo Y., Kinoshita K., Kou T., Haga H., Ikai I., Uemoto S., Chiba T. Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. Hepatology 2008, 47:888-896.
71. Kotani A., Okazaki I.M., Muramatsu M., Kinoshita K., Begum N.A., Nakajima T., Saito H., Honjo T. A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression. Proc. Natl. Acad. Sci. USA 2005, 102:4506-4511.
72. Kou T., Marusawa H., Kinoshita K., Endo Y., Okazaki I.M., Ueda Y., Kodama Y., Haga H., Ikai I., Chiba T. Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis. Int. J. Cancer 2007, 120:469-476.
73. Lebecque S.G., Gearhart P.J. Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1 kb from V(D)J gene. J. Exp. Med. 1990, 172:1717-1727.
74. Lengauer C., Kinzler K.W., Vogelstein B. Genetic instabilities in human cancers. Nature 1998, 396:643-649.
75. Li G., Alt F.W., Cheng H.L., Brush J.W., Goff P.H., Murphy M.M., Franco S., Zhang Y., Zha S. Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination. Mol. Cell 2008, 31:631-640.
76. Liu M., Schatz D.G. Balancing AID and DNA repair during somatic hypermutation. Trends Immunol. 2009, 30:173-181.
77. Liu M., Duke J.L., Richter D.J., Vinuesa C.G., Goodnow C.C., Kleinstein S.H., Schatz D.G. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451:841-845.
78. Liu T.Y., Chen S.U., Kuo S.H., Cheng A.L., Lin C.W. E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and stronger expression of the memory B-cell-associated miR-223: Possible correlation with stage and treatment response. Mod. Pathol. 2010, 23:1507-1517.
79. Longerich S., Tanaka A., Bozek G., Nicolae D., Storb U. The very 5' end and the constant region of Ig genes are spared from somatic mutation because AID does not access these regions. J. Exp. Med. 2005, 202:1443-1454.
80. Longerich S., Basu U., Alt F., Storb U. AID in somatic hypermutation and class switch recombination. Curr. Opin. Immunol. 2006, 18:164-174.
81. Ma Y., Lu H., Schwarz K., Lieber M.R. Repair of double-strand DNA breaks by the human nonhomologous DNA end joining pathway: The iterative processing model. Cell Cycle 2005, 4:1193-1200.
82. Machida K., Cheng K.T., Sung V.M., Shimodaira S., Lindsay K.L., Levine A.M., Lai M.Y., Lai M.M. Hepatitis C virus induces a mutator phenotype: Enhanced mutations of immunoglobulin and protooncogenes. Proc. Natl. Acad. Sci. USA 2004, 101:4262-4267.
83. Machida K., Cheng K.T., Pavio N., Sung V.M., Lai M.M. Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells. J. Virol. 2005, 79:8079-8089.
84. Maki R., Traunecker A., Sakano H., Roeder W., Tonegawa S. Exon shuffling generates an immunoglobulin heavy chain gene. Proc. Natl. Acad. Sci. USA 1980, 77:2138-2142.
85. 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.
86. Manis J.P., Tian M., Alt F.W. Mechanism and control of class-switch recombination. Trends Immunol. 2002, 23:31-39.
87. Martin A., Scharff M.D. AID and mismatch repair in antibody diversification. Nat. Rev. Immunol. 2002, 2:605-614.
88. Martomo S.A., Fu D., Yang W.W., Joshi N.S., Gearhart P.J. Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from cells expressing activation-induced cytidine deaminase. J. Immunol. 2005, 174:7787-7791.
89. Marusawa H. Aberrant AID expression and human cancer development. Int. J. Biochem. Cell Biol. 2008, 40:1399-1402.
90. Marusawa H., Chiba T. Helicobacter pylori-induced activation-induced cytidine deaminase expression and carcinogenesis. Curr. Opin. Immunol. 2010, 22:442-447.
91. Marusawa H., Hijikata M., Chiba T., Shimotohno K. Hepatitis C virus core protein inhibits Fas- and tumor necrosis factor alpha-mediated apoptosis via NF-kappaB activation. J. Virol. 1999, 73:4713-4720.
92. Matsumoto Y., Marusawa H., Kinoshita K., Endo Y., Kou T., Morisawa T., Azuma T., Okazaki I.M., Honjo T., Chiba T. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat. Med. 2007, 13:470-476.
93. Matsumoto Y., Marusawa H., Kinoshita K., Niwa Y., Sakai Y., Chiba T. Up-regulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. Gastroenterology 2010, 139:1984-1994.
94. Matsuoka M., Yoshida K., Maeda T., Usuda S., Sakano H. Switch circular DNA formed in cytokine-treated mouse splenocytes: Evidence for intramolecular DNA deletion in immunoglobulin class switching. Cell 1990, 62:135-142.
95. McBride K.M., Barreto V., Ramiro A.R., Stavropoulos P., Nussenzweig M.C. Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J. Exp. Med. 2004, 199:1235-1244.
96. McBride K.M., Gazumyan A., Woo E.M., Barreto V.M., Robbiani D.F., Chait B.T., Nussenzweig M.C. Regulation of hypermutation by activation-induced cytidine deaminase phosphorylation. Proc. Natl. Acad. Sci. USA 2006, 103:8798-8803.
97. McBride K.M., Gazumyan A., Woo E.M., Schwickert T.A., Chait B.T., Nussenzweig M.C. Regulation of class switch recombination and somatic mutation by AID phosphorylation. J. Exp. Med. 2008, 205:2585-2594.
98. Min I.M., Rothlein L.R., Schrader C.E., Stavnezer J., Selsing E. Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2. J. Exp. Med. 2005, 201:1885-1890.
99. Miyazono K., Suzuki H., Imamura T. Regulation of TGF-beta signaling and its roles in progression of tumors. Cancer Sci. 2003, 94:230-234.
100. Morisawa T., Marusawa H., Ueda Y., Iwai A., Okazaki I.M., Honjo T., Chiba T. Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. Int. J. Cancer 2008, 123:2735-2740.
101. Muramatsu M., Honjo T. Complex layers of genetic alteration in the generation of antibody diversity. Trends Immunol. 2001, 22:66-68.
102. Muramatsu M., Sankaranand V.S., Anant S., Sugai M., Kinoshita K., Davidson N.O., Honjo T. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J. Biol. Chem. 1999, 274:18470-18476.
103. Muramatsu M., Kinoshita K., Fagarasan S., Yamada S., Shinkai Y., Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 2000, 102:553-563.
104. Muramatsu M., Nagaoka H., Shinkura R., Begum N.A., Honjo T. Discovery of activation-induced cytidine deaminase, the engraver of antibody memory. Adv. Immunol. 2007, 94:1-36.
105. Muto T., Okazaki I.M., Yamada S., Tanaka Y., Kinoshita K., Muramatsu M., Nagaoka H., Honjo T. Negative regulation of activation-induced cytidine deaminase in B cells. Proc. Natl. Acad. Sci. USA 2006, 103:2752-2757.
106. Nagaoka H., Tran T.H., Kobayashi M., Aida M., Honjo T. Preventing AID, a physiological mutator, from deleterious activation: Regulation of the genomic instability that is associated with antibody diversity. Int. Immunol. 2010, 22:227-235.
107. Neuberger M.S., Harris R.S., Di Noia J., Petersen-Mahrt S.K. Immunity through DNA deamination. Trends Biochem. Sci. 2003, 28:305-312.
108. Neuberger M.S., Di Noia J.M., Beale R.C., Williams G.T., Yang Z., Rada C. Somatic hypermutation at A.T pairs: Polymerase error versus dUTP incorporation. Nat. Rev. Immunol. 2005, 5:171-178.
109. Nowak U., Matthews A.J., Zheng S., Chaudhuri J. The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nat. Immunol. 2011, 12:160-166.
110. Nussenzweig A., Nussenzweig M.C. Origin of chromosomal translocations in lymphoid cancer. Cell 2010, 141:27-38.
111. Odegard V.H., Schatz D.G. Targeting of somatic hypermutation. Nat. Rev. Immunol. 2006, 6:573-583.
112. Ohnishi N., Yuasa H., Tanaka S., Sawa H., Miura M., Matsui A., Higashi H., Musashi M., Iwabuchi K., Suzuki M., Yamada G., Azuma T., et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. Natl. Acad. Sci. USA 2008, 105:1003-1008.
113. Okazaki I.M., Hiai H., Kakazu N., Yamada S., Muramatsu M., Kinoshita K., Honjo T. Constitutive expression of AID leads to tumorigenesis. J. Exp. Med. 2003, 197:1173-1181.
114. Orthwein A., Patenaude A.M., Affar el B., Lamarre A., Young J.C., Di Noia J.M. Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90. J. Exp. Med. 2010, 207:2751-2765.
115. Pan-Hammarstrom Q., Jones A.M., Lahdesmaki A., Zhou W., Gatti R.A., Hammarstrom L., Gennery A.R., Ehrenstein M.R. Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells. J. Exp. Med. 2005, 201:189-194.
116. Papavasiliou F.N., Schatz D.G. Somatic hypermutation of immunoglobulin genes: Merging mechanisms for genetic diversity. Cell 2002, 109(Suppl.):S35-S44.
117. Park S.R., Zan H., Pal Z., Zhang J., Al-Qahtani A., Pone E.J., Xu Z., Mai T., Casali P. HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. Nat. Immunol. 2009, 10:540-550.
118. Pasqualucci L., Neumeister P., Goossens T., Nanjangud G., Chaganti R.S., Kuppers R., Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001, 412:341-346.
119. Pasqualucci L., Guglielmino R., Houldsworth J., Mohr J., Aoufouchi S., Polakiewicz R., Chaganti R.S., Dalla-Favera R. Expression of the AID protein in normal and neoplastic B cells. Blood 2004, 104:3318-3325.
120. Pasqualucci L., Kitaura Y., Gu H., Dalla-Favera R. PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells. Proc. Natl. Acad. Sci. USA 2006, 103:395-400.
121. Pasqualucci L., Bhagat G., Jankovic M., Compagno M., Smith P., Muramatsu M., Honjo T., Morse H.C., Nussenzweig M.C., Dalla-Favera R. AID is required for germinal center-derived lymphomagenesis. Nat. Genet. 2008, 40:108-112.
122. Pauklin S., Petersen-Mahrt S.K. Progesterone inhibits activation-induced deaminase by binding to the promoter. J. Immunol. 2009, 183:1238-1244.
123. Pauklin S., Sernandez I.V., Bachmann G., Ramiro A.R., Petersen-Mahrt S.K. Estrogen directly activates AID transcription and function. J. Exp. Med. 2009, 206:99-111.
124. Pavri R., Gazumyan A., Jankovic M., Di Virgilio M., Klein I., Ansarah-Sobrinho C., Resch W., Yamane A., Reina San-Martin B., Barreto V., Nieland T.J., Root D.E., et al. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 2010, 143:122-133.
125. Peled J.U., Kuang F.L., Iglesias-Ussel M.D., Roa S., Kalis S.L., Goodman M.F., Scharff M.D. The biochemistry of somatic hypermutation. Annu. Rev. Immunol. 2008, 26:481-511.
126. Peled J.U., Sellers R.S., Iglesias-Ussel M.D., Shin D.M., Montagna C., Zhao C., Li Z., Edelmann W., Morse H.C., Scharff M.D. Msh6 protects mature B cells from lymphoma by preserving genomic stability. Am. J. Pathol. 2010, 177:2597-2608.
127. Peters A., Storb U. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 1996, 4:57-65.
128. Petersen-Mahrt S.K., Harris R.S., Neuberger M.S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 2002, 418:99-103.
129. Pham P., Bransteitter R., Petruska J., Goodman M.F. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 2003, 424:103-107.
130. Pikarsky E., Porat R.M., Stein I., Abramovitch R., Amit S., Kasem S., Gutkovich-Pyest E., Urieli-Shoval S., Galun E., Ben-Neriah Y. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004, 431:461-466.
131. Powell L.M., Wallis S.C., Pease R.J., Edwards Y.H., Knott T.J., Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 1987, 50:831-840.
132. Rabbitts T.H., Forster A., Dunnick W., Bentley D.L. The role of gene deletion in the immunoglobulin heavy chain switch. Nature 1980, 283:351-356.
133. Rada C., Milstein C. The intrinsic hypermutability of antibody heavy and light chain genes decays exponentially. EMBO J. 2001, 20:4570-4576.
134. Rada C., Yelamos J., Dean W., Milstein C. The 5' hypermutation boundary of kappa chains is independent of local and neighbouring sequences and related to the distance from the initiation of transcription. Eur. J. Immunol. 1997, 27:3115-3120.
135. Rada C., Williams G.T., Nilsen H., Barnes D.E., Lindahl T., Neuberger M.S. Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr. Biol. 2002, 12:1748-1755.
136. Ramiro A.R., Stavropoulos P., Jankovic M., Nussenzweig M.C. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nat. Immunol. 2003, 4:452-456.
137. Ramiro A.R., Jankovic M., Eisenreich T., Difilippantonio S., Chen-Kiang S., Muramatsu M., Honjo T., Nussenzweig A., Nussenzweig M.C. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 2004, 118:431-438.
138. Ramiro A.R., Jankovic M., Callen E., Difilippantonio S., Chen H.T., McBride K.M., Eisenreich T.R., Chen J., Dickins R.A., Lowe S.W., Nussenzweig A., Nussenzweig M.C. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature 2006, 440:105-109.
139. Reina-San-Martin B., Difilippantonio S., Hanitsch L., Masilamani R.F., Nussenzweig A., Nussenzweig M.C. H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J. Exp. Med. 2003, 197:1767-1778.
140. Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., Catalan N., Forveille M., Dufourcq-Labelouse R., Gennery A., Tezcan I., Ersoy F., et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the hyper-IgM syndrome (HIGM2). Cell 2000, 102:565-575.
141. Robbiani D.F., Bothmer A., Callen E., Reina-San-Martin B., Dorsett Y., Difilippantonio S., Bolland D.J., Chen H.T., Corcoran A.E., Nussenzweig A., Nussenzweig M.C. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell 2008, 135:1028-1038.
142. Rogozin I.B., Diaz M. Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process. J. Immunol. 2004, 172:3382-3384.
143. Rooney S., Chaudhuri J., Alt F.W. The role of the non-homologous end-joining pathway in lymphocyte development. Immunol. Rev. 2004, 200:115-131.
144. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature 1980, 286:676-683.
145. Sayegh C.E., Quong M.W., Agata Y., Murre C. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat. Immunol. 2003, 4:586-593.
146. Schrader C.E., Linehan E.K., Mochegova S.N., Woodland R.T., Stavnezer J. Inducible DNA breaks in Ig S regions are dependent on AID and UNG. J. Exp. Med. 2005, 202:561-568.
147. Schrader C.E., Guikema J.E., Linehan E.K., Selsing E., Stavnezer J. 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. 2007, 179:6064-6071.
148. Shen H.M., Storb U. Activation-induced cytidine deaminase (AID) can target both DNA strands when the DNA is supercoiled. Proc. Natl. Acad. Sci. USA 2004, 101:12997-13002.
149. Shimizu A., Takahashi N., Yaoita Y., Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell 1982, 28:499-506.
150. Sjoblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314:268-274.
151. Smith D.S., Creadon G., Jena P.K., Portanova J.P., Kotzin B.L., Wysocki L.J. Di- and trinucleotide target preferences of somatic mutagenesis in normal and autoreactive B cells. J. Immunol. 1996, 156:2642-2652.
152. Sonoda E., Hochegger H., Saberi A., Taniguchi Y., Takeda S. Differential usage of non-homologous end-joining and homologous recombination in double strand break repair. DNA Repair (Amst.) 2006, 5:1021-1029.
153. Soulas-Sprauel P., Le Guyader G., Rivera-Munoz P., Abramowski V., Olivier-Martin C., Goujet-Zalc C., Charneau P., de Villartay J.P. Role for DNA repair factor XRCC4 in immunoglobulin class switch recombination. J. Exp. Med. 2007, 204:1717-1727.
154. Stavnezer J., Schrader C.E. Mismatch repair converts AID-instigated nicks to double-strand breaks for antibody class-switch recombination. Trends Genet. 2006, 22:23-28.
155. Stavnezer J., Guikema J.E., Schrader C.E. Mechanism and regulation of class switch recombination. Annu. Rev. Immunol. 2008, 26:261-292.
156. Storb U. Progress in understanding the mechanism and consequences of somatic hypermutation. Immunol. Rev. 1998, 162:5-11.
157. Strober W., Fuss I., Mannon P. The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 2007, 117:514-521.
158. Takai A., Toyoshima T., Uemura M., Kitawaki Y., Marusawa H., Hiai H., Yamada S., Okazaki I.M., Honjo T., Chiba T., Kinoshita K. A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. Oncogene 2009, 28:469-478.
159. Takaori-Kondo A. APOBEC family proteins: Novel antiviral innate immunity. Int. J. Hematol. 2006, 83:213-216.
160. Tanaka Y., Marusawa H., Seno H., Matsumoto Y., Ueda Y., Kodama Y., Endo Y., Yamauchi J., Matsumoto T., Takaori-Kondo A., Ikai I., Chiba T. Anti-viral protein APOBEC3G is induced by interferon-alpha stimulation in human hepatocytes. Biochem. Biophys. Res. Commun. 2006, 341:314-319.
161. Teng G., Hakimpour P., Landgraf P., Rice A., Tuschl T., Casellas R., Papavasiliou F.N. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 2008, 28:621-629.
162. Tian M., Alt F.W. Transcription-induced cleavage of immunoglobulin switch regions by nucleotide excision repair nucleases in vitro. J. Biol. Chem. 2000, 275:24163-24172.
163. Tilg H., Wilmer A., Vogel W., Herold M., Nolchen B., Judmaier G., Huber C. Serum levels of cytokines in chronic liver diseases. Gastroenterology 1992, 103:264-274.
164. Tippin B., Goodman M.F. A new class of errant DNA polymerases provides candidates for somatic hypermutation. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001, 356:47-51.
165. Tran T.H., Nakata M., Suzuki K., Begum N.A., Shinkura R., Fagarasan S., Honjo T., Nagaoka H. B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers. Nat. Immunol. 2010, 11:148-154.
166. von Schwedler U., Jack H.M., Wabl M. Circular DNA is a product of the immunoglobulin class switch rearrangement. Nature 1990, 345:452-456.
167. Wilson T.M., Vaisman A., Martomo S.A., Sullivan P., Lan L., Hanaoka F., Yasui A., Woodgate R., Gearhart P.J. MSH2-MSH6 stimulates DNA polymerase eta, suggesting a role for A:T mutations in antibody genes. J. Exp. Med. 2005, 201:637-645.
168. Xue K., Rada C., Neuberger M.S. The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2-/- ung-/- mice. J. Exp. Med. 2006, 203:2085-2094.
169. Yadav A., Olaru A., Saltis M., Setren A., Cerny J., Livak F. Identification of a ubiquitously active promoter of the murine activation-induced cytidine deaminase (AICDA) gene. Mol. Immunol. 2006, 43:529-541.
170. Yamane A., Resch W., Kuo N., Kuchen S., Li Z., Sun H.W., Robbiani D.F., McBride K., Nussenzweig M.C., Casellas R. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat. Immunol. 2011, 12:62-69.
171. Yoshikawa K., Okazaki I.M., Eto T., Kinoshita K., Muramatsu M., Nagaoka H., Honjo T. AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science 2002, 296:2033-2036.
172. Yu K., Lieber M.R. Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism. DNA Repair (Amst.) 2003, 2:1163-1174.