AID and Apobec3G haphazard deamination and mutational diversity

Cellular and Molecular Life Sciences

Volumn 70, Issue 17, 2013, Pages 3089-3108

  Jaszczur, Malgorzata ^a   Bertram, Jeffrey G ^a   Pham, Phuong ^a   Scharff, Matthew D ^b   Goodman, Myron F ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Activation induced deoxycytidine deaminase (AID); Apo3G; HIV 1 inactivation; Ig diversity; Somatic hypermutation; ssDNA scanning

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; ACTIVATION INDUCED DEOXYCYTIDINE DEAMINASE; APOLIPOPROTEIN B MESSENGER RNA EDITING ENZYME CATALYTIC POLYPEPTIDE 3G; IMMUNOGLOBULIN; SINGLE STRANDED DNA; UNCLASSIFIED DRUG;

AQUEOUS SOLUTION; B LYMPHOCYTE; COMPLEX FORMATION; DEAMINATION; DNA DETERMINATION; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME LOCALIZATION; ENZYME REGULATION; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE REARRANGEMENT; GENETIC TRANSCRIPTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYPER IGM SYNDROME; MOLECULAR PATHOLOGY; MUTATIONAL ANALYSIS; NONHUMAN; NUCLEOTIDE MOTIF; PROTEIN DNA INTERACTION; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; SOMATIC HYPERMUTATION; T LYMPHOCYTE; VIRUS CELL INTERACTION;

ANTIBODY DIVERSITY; B-LYMPHOCYTES; CYTIDINE DEAMINASE; DEAMINATION; DRUG DELIVERY SYSTEMS; GENETIC VARIATION; HUMANS; MUTATION; SINGLE-CHAIN ANTIBODIES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84882452347     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-012-1212-1     Document Type: Review

References (214)

1. Milstein C (1987) Diversity and the genesis of high affinity antibodies. Biochem Soc Trans 15:779-787
2. Schatz DG, Swanson PC (2011) V(D)J recombination: mechanisms of initiation. Annu Rev Genet 45:167-202
3. Rajewsky K (1996) Clonal selection and learning in the antibody system. Nature 381:751-758
4. Peled JU, Kuang FL, Iglesias-Ussel MD, Roa S, Kalis SL, Goodman MF, Scharff MD (2008) The biochemistry of somatic hypermutation. Annu Rev Immunol 26:481-511
5. Stavnezer J, Guikema JE, Schrader CE (2008) Mechanism and regulation of class switch recombination. Annu Rev Immunol 26:261-292
6. Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO, Honjo T (1999) 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 274:18470-18476
7. 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 102:553-563
8. Reynaud CA, Delbos F, Faili A, Gueranger Q, Aoufouchi S, Weill JC (2009) Competitive repair pathways in immunoglobulin gene hypermutation. Philos Trans R Soc Lond B 364:613-619
9. Teng G, Papavasiliou FN (2007) Immunoglobulin somatic hypermutation. Annu Rev Genet 41:107-120
10. Chahwan R, Edelmann W, Scharff MD, Roa S (2012) AIDing antibody diversity by error-prone mismatch repair. Semin Immunol 24:293-300
11. Xu Z, Zan H, Pone EJ, Mai T, Casali P (2012) Immunoglobulin class-switch DNA recombination: induction, targeting and beyond. Nat Rev Immunol 12:517-531
12. Prochnow C, Bransteitter R, Chen XS (2009) APOBEC deaminases-mutases with defensive roles for immunity. Sci China C Life Sci 52:893-902
13. Chelico L, Pham P, Petruska J, Goodman MF (2009) Biochemical basis of immunological and retroviral responses to DNA-targeted cytosine deamination by activation-induced cytidine deaminase and APOBEC3G. J Biol Chem 284:27761-27765
14. Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646-650
15. Chiu YL, Greene WC (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annu Rev Immunol 26:317-353
16. Pham P, Bransteitter R, Petruska J, Goodman MF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424:103-107
17. Pham P, Calabrese P, Park SJ, Goodman MF (2011) Analysis of a single-stranded DNA-scanning process in which activation-induced deoxycytidine deaminase (AID) deaminates C to U haphazardly and inefficiently to ensure mutational diversity. J Biol Chem 286:24931-24942
18. Chelico L, Pham P, Calabrese P, Goodman MF (2006) APOBEC3G DNA deaminase acts processively 3′ → 5′ on single-stranded DNA. Nat Struct Mol Biol 13:392-399
19. Chelico L, Prochnow C, Erie DA, Chen XS, Goodman MF (2010) Structural model for deoxycytidine deamination mechanisms of the HIV-1 inactivation enzyme APOBEC3G. J Biol Chem 285:16195-16205
20. Chelico L, Sacho EJ, Erie DA, Goodman MF (2008) A model for oligomeric regulation of APOBEC3G cytosine deaminase-dependent restriction of HIV. J Biol Chem 283:13780-13791
21. Conticello SG, Langlois MA, Yang Z, Neuberger MS (2007) DNA deamination in immunity: aID in the context of its APOBEC relatives. Adv Immunol 94:37-73
22. Durandy A (2009) Immunoglobulin class switch recombination: study through human natural mutants. Philos Trans R Soc Lond B 364:577-582
23. Gorman J, Chowdhury A, Surtees JA, Shimada J, Reichman DR, Alani E, Greene EC (2007) Dynamic basis for one-dimensional DNA scanning by the mismatch repair complex Msh2-Msh6. Mol Cell 28:359-370
24. Blainey PC, Luo G, Kou SC, Mangel WF, Verdine GL, Bagchi B, Xie XS (2009) Nonspecifically bound proteins spin while diffusing along DNA. Nat Struct Mol Biol 16:1224-1229
25. Blainey PC, van Oijen AM, Banerjee A, Verdine GL, Xie XS (2006) A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proc Natl Acad Sci USA 103:5752-5757
26. Porecha RH, Stivers JT (2008) Uracil DNA glycosylase uses DNA hopping and short-range sliding to trap extrahelical uracils. Proc Natl Acad Sci USA 105:10791-10796
27. Bennett SE, Sanderson RJ, Mosbaugh DW (1995) Processivity of Escherichia coli and rat liver mitochondrial uracil-DNA glycosylase is affected by NaCl concentration. Biochemistry 34:6109-6119
28. Schonhoft JD, Stivers JT (2012) Timing facilitated site transfer of an enzyme on DNA. Nat Chem Biol 8:205-210
29. Friedman JI, Stivers JT (2010) Detection of damaged DNA bases by DNA glycosylase enzymes. Biochemistry 49:4957-4967
30. Jeltsch A, Pingoud A (1998) Kinetic characterization of linear diffusion of the restriction endonuclease EcoRV on DNA. Biochemistry 37:2160-2169
31. Gowers DM, Wilson GG, Halford SE (2005) Measurement of the contributions of 1D and 3D pathways to the translocation of a protein along DNA. Proc Natl Acad Sci USA 102:15883-15888
32. Bonnet I et al (2008) Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA. Nucleic Acids Res 36:4118-4127
33. van den Broek B, Lomholt MA, Kalisch S-MJ, Metzler R, Wiuite GJL (2008) How DNA coiling enhances target localization by proteins. Proc Natl Acad Sci USA 105:15738-15742
34. Revy P et al (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102:565-575
35. Storb U et al (1999) Molecular aspects of somatic hypermutation of immunoglobulin genes. Cold Spring Harb Symp Quant Biol 64:227-234
36. Yoshikawa K, Okazaki IM, Eto T, Kinoshita K, Muramatsu M, Nagaoka H, Honjo T (2002) AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science 296:2033-2036
37. Chaudhuri J, Tian M, Khuong C, Chua K, Pinaud E, Alt FW (2003) Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422:726-730
38. Sohail A, Klapacz J, Samaranayake M, Ullah A, Bhagwat AS (2003) Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations. Nucl Acids Res 31:2990-2994
39. Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC (2003) Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nat Immunol 4:452-456
40. Shen HM, Ratnam S, Storb U (2005) Targeting of the activation-induced cytosine deaminase is strongly influenced by the sequence and structure of the targeted DNA. Mol Cell Biol 25:10815-10821
41. Di Noia JM, Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76:1-22
42. Rada C, Di Noia JM, Neuberger MS (2004) Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol Cell 16:163-171
43. Longerich S, Tanaka A, Bozek G, Nicolae D, Storb U (2005) 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 202:1443-1454
44. Xue K, Rada C, Neuberger MS (2006) The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2-/- ung-/- mice. J Exp Med 203:2085-2094
45. Li Z et al (2004) Examination of Msh6- and Msh3-deficient mice in class switching reveals overlapping and distinct roles of mutS homologues in antibody diversification. J Exp Med 200:47-59
46. Shen HM, Tanaka A, Bozek G, Nicolae D, Storb U (2006) Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice. J Immunol 177:5386-5392
47. Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, Kleinstein SH, Schatz DG (2008) Two levels of protection for the B cell genome during somatic hypermutation. Nature 451:841-845
48. Gordon MS, Kanegai CM, Doerr JR, Wall R (2003) Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a). Proc Natl Acad Sci USA 100:4126-4131
49. Muschen M, Re D, Jungnickel B, Diehl V, Rajewsky K, Kuppers R (2000) Somatic mutation of the CD95 gene in human B cells as a side-effect of the germinal center reaction. J Exp Med 192:1833-1840
50. Pasqualucci L et al (1998) BCL-6 Mutations in Normal Germinal Center B Cells: evidence of Somatic Hypermutation Acting Outside Ig Loci. Proc Natl Acad Sci USA 95:11816-11821
51. Shen HM, Peters A, Baron B, Zhu X, Storb U (1998) Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 280:1750-1752
52. Kotani A, Okazaki IM, Muramatsu M, Kinoshita K, Begum NA, Nakajima T, Saito H, Honjo T (2005) 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 102:4506-4511
53. Yamane A et al (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
54. Hogenbirk MA, Velds A, Kerkhoven RM, Jacobs H (2012) Reassessing genomic targeting of AID. Nat Immunol 13:797-798
55. Pavri R et al (2010) Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143:122-133
56. Yamane A, Resch W, Nussezweig M, Casellas R (2012) Reply to "Reassessing genomic targeting of AID". Nat Immunol 13:798-800
57. Peron S et al (2012) AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells. Science 336:931-934
58. Klein IA et al (2011) Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147:95-106
59. Jiang Y, Soong TD, Wang L, Melnick AM, Elemento O (2012) Genome-wide detection of genes targeted by non-Ig somatic hypermutation in lymphoma. PLoS ONE 7:e40332
60. Kato L et al (2012) Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. Proc Natl Acad Sci USA 109:2479-2484
61. Betz AG, Milstein C, Gonzalez-Fernandez A, Pannell R, Larson T, Neuberger MS (1994) Elements regulating somatic hypermutation of an immunoglobulin kappa gene: critical role for the intron enhancer/matrix attachment region. Cell 77:239-248
62. Lebecque SG, Gearhart PJ (1990) 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 172:1717-1727
63. Rada C, Gonzalez-Fernandez A, Jarvis JM, Milstein C (1994) The 5′ boundary of somatic hypermutation in a V kappa gene is in the leader intron. Eur J Immunol 24:1453-1457
64. Hackett JJ, Rogerson BJ, O'Brien RL, Storb U (1990) Analysis of somatic mutations in kappa transgenes. J Exp Med 172:131-137
65. Weber JS, Berry J, Manser T, Claflin JL (1991) Position of the rearranged V kappa and its 5′ flanking sequences determines the location of somatic mutations in the J kappa locus. J Immunol 146:3652-3655
66. Storb U, Peters A, Klotz E, Kim N, Shen HM, Kage K, Rogerson B, Martin TE (1998) Somatic hypermutation of immunoglobulin genes is linked to transcription. Curr Top Microbiol Immunol 229:11-19
67. Peters A, Storb U (1996) Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 4:57-65
68. Tumas-Brundage K, Manser T (1997) The transcriptional promoter regulates hypermutation of the antibody heavy chain locus. J Exp Med 185:239-250
69. Goyenechea B, Klix N, Yélamos J, Williams GT, Riddell A, Neuberger MS, Milstein C (1997) Cells highly expressing Igk transgenes show clonal recruitment of hypermutation: a role for both MAR and the enhancers. EMBO J 16:3987-3994
70. Fukita Y, Jacobs H, Rajewsky K (1998) Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 9:105-114
71. Bachl J, Carlson C, Gray-Schopfer V, Dessing M, Olsson C (2001) Increased transcription levels induce higher mutation rates in a hypermutating cell line. J Immunol 166:5051-5057
72. Ronai D, Iglesias-Ussel MD, Fan M, Li Z, Martin A, Scharff MD (2007) Detection of chromatin-associated single-stranded DNA in regions targeted for somatic hypermutation. J Exp Med 204:181-190
73. Perlot T, Li G, Alt FW (2008) Antisense transcripts from immunoglobulin heavy-chain locus V(D)J and switch regions. Proc Natl Acad Sci USA 105:3843-3848
74. Basu U et al (2011) The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates. Cell 144:353-363
75. Shen HM, Storb U (2004) Activation-induced cytidine deaminase (AID) can target both DNA strands when the DNA is supercoiled. Proc Natl Acad Sci USA 101:12997-13002
76. Shockett P, Stavnezer J (1991) Effect of cytokines on switching to IgA and alpha germline transcripts in the B lymphoma I.29 mu. Transforming growth factor-beta activates transcription of the unrearranged C alpha gene. J Immunol 147:4374-4383
77. Lutzker S, Rothman P, Pollock R, Coffman R, Alt FW (1988) Mitogen- and IL-4-regulated expression of germ-line Ig gamma 2b transcripts: evidence for directed heavy chain class switching. Cell 53:177-184
78. Snapper CM, Paul WE (1987) Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236:944-947
79. Jung S, Rajewsky K, Radbruch A (1993) Shutdown of class switch recombination by deletion of a switch region control element. Science 259:984-987
80. Zhang J, Bottaro A, Li S, Stewart V, Alt FW (1993) A selective defect in IgG2b switching as a result of targeted mutation of the I gamma 2b promoter and exon. EMBO J 12:3529-3537
81. Huang FT, Yu K, Balter BB, Selsing E, Oruc Z, Khamlichi AA, Hsieh CL, Lieber MR (2007) Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch region. Mol Cell Biol 27:5921-5932
82. Yu K, Chedin F, Hsieh CL, Wilson TE, Lieber MR (2003) R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat Immunol 4:442-451
83. Zarrin AA, Alt FW, Chaudhuri J, Stokes N, Kaushal D, Du Pasquier L, Tian M (2004) An evolutionarily conserved target motif for immunoglobulin class-switch recombination. Nat Immunol 5:1275-1281
84. Yelamos J et al (1995) Targeting of non-Ig sequences in place of the V segment by somatic hypermutation. Nature 376:225-229
85. MacCarthy T, Kalis SL, Roa S, Pham P, Goodman MF, Scharff MD, Bergman A (2009) V-region mutation in vitro, in vivo, and in silico reveal the importance of the enzymatic properties of AID and the sequence environment. Proc Natl Acad Sci USA 106:8629-8634
86. Luby TM, Schrader CE, Stavnezer J, Selsing E (2001) The MU switch region tandem repeats are important, but not required, for antibody class switch recombination. J Exp Med 193:159-168
87. Khamlichi AA, Glaudet F, Oruc Z, Denis V, Le Bert M, Cogne M (2004) Immunoglobulin class-switch recombination in mice devoid of any Smicro tandem repeat. Blood 103:3828-3836
88. Xu Z et al (2010) 14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′-rich switch regions for class switch recombination. Nat Struct Mol Biol 17:1124-1135
89. Maizels N (2005) Immunoglobulin gene diversification. Annu Rev Genet 39:23-46
90. Klotz EL, Storb U (1996) Somatic hypermutation of a lambda 2 transgene under the control of the lambda enhancer or the heavy chain intron enhancer. J Immunol 157:4458-4463
91. Bachl J, Olsson C, Chitkara N, Wabl M (1998) The Ig mutator is dependent on the presence, position, and orientation of the large intron enhancer. Proc Natl Acad Sci USA 95:2396-2399
92. Komori A, Xu Z, Wu X, Zan H, Casali P (2006) Biased dA/dT somatic hypermutation as regulated by the heavy chain intronic iEmu enhancer and 3′Ealpha enhancers in human lymphoblastoid B cells. Mol Immunol 43:1817-1826
93. Ronai D, Iglesias-Ussel MD, Fan M, Shulman MJ, Scharff MD (2005) Complex regulation of somatic hypermutation by cis-acting sequences in the endogenous IgH gene in hybridoma cells. Proc Natl Acad Sci USA 102:11829-11834
94. Morvan CL, Pinaud E, Decourt C, Cuvillier A, Cogne M (2003) The immunoglobulin heavy-chain locus hs3b and hs4 3′ enhancers are dispensable for VDJ assembly and somatic hypermutation. Blood 102:1421-1427
95. Pinaud E, Marquet M, Fiancette R, Peron S, Vincent-Fabert C, Denizot Y, Cogne M (2011) The IgH locus 3′ regulatory region: pulling the strings from behind. Adv Immunol 110:27-70
96. Michael N, Shen HM, Longerich S, Kim N, Longacre A, Storb U (2003) The E box motif CAGGTG enhances somatic hypermutation without enhancing transcription. Immunity 19:235-242
97. Tanaka A, Shen HM, Ratnam S, Kodgire P, Storb U (2010) Attracting AID to targets of somatic hypermutation. J Exp Med 207:405-415
98. Conlon TM, Meyer KB (2006) The chicken Ig light chain 3′-enhancer is essential for gene expression and regulates gene conversion via the transcription factor E2A. Eur J Immunol 36:139-148
99. Schoetz U, Cervelli M, Wang YD, Fiedler P, Buerstedde JM (2006) E2A expression stimulates Ig hypermutation. J Immunol 177:395-400
100. Okazaki IM, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K, Honjo T (2003) Constitutive expression of AID leads to tumorigenesis. J Exp Med 197:1173-1181
101. Martin A, Scharff MD (2002) Somatic hypermutation of the AID transgene in B and non-B cells. Proc Natl Acad Sci USA 99:12304-12308
102. Larijani M, Petrov AP, Kolenchenko O, Berru M, Krylov SN, Martin A (2007) AID associates with single-stranded DNA with high affinity and a long complex half-life in a sequence-independent manner. Mol Cell Biol 27:20-30
103. Mu Y, Prochnow C, Pham P, Chen XS, Goodman MF (2012) A structural basis for the biochemical behavior of activation-induced deoxycytidine deaminase class-switch recombination-defective hyper-IgM-2 mutants. J Biol Chem 287:28007-28016
104. Nambu Y, Sugai M, Gonda H, Lee C, Katakai T, Agata Y, Yokota Y, Shimizu A (2003) Transcription-coupled events associating with immunoglobulin switch region chromatin. Science 302:2137-2140
105. Jeevan-Raj BP et al (2011) Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. J Exp Med 208:1649-1660
106. Ranjit S, Khair L, Linehan EK, Ucher AJ, Chakrabarti M, Schrader CE, Stavnezer J (2011) AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus. J Immunol 187:2464-2475
107. Conticello SG, Ganesh K, Xue K, Lu M, Rada C, Neuberger MS (2008) Interaction between antibody-diversification enzyme AID and spliceosome- associated factor CTNNBL1. Mol Cell 31:474-484
108. Nowak U, Matthews AJ, Zheng S, Chaudhuri J (2010) The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nat Immunol 12:160-166
109. Kanehiro Y et al (2012) Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF1. Proc Natl Acad Sci USA 109:1216-1221
110. Maeda K, Singh SK, Eda K, Kitabatake M, Pham P, Goodman MF, Sakaguchi N (2010) GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region DNA. J Biol Chem 285:23945-23953
111. Chaudhuri J, Khuong C, Alt FW (2004) Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 430:992-998
112. Wu X, Geraldes P, Platt JL, Cascalho M (2005) The double-edged sword of activation-induced cytidine deaminase. J Immunol 174:934-941
113. Vuong BQ, Lee M, Kabir S, Irimia C, Macchiarulo S, McKnight GS, Chaudhuri J (2009) Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination. Nat Immunol 10:420-426
114. Kuang FL, Luo Z, Scharff MD (2009) H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination. Proc Natl Acad Sci USA 106:5288-5293
115. Kodgire P, Mukkawar P, North JA, Poirier MG, Storb U (2012) Nucleosome stability dramatically impacts the targeting of somatic hypermutation. Mol Cell Biol 32:2030-2040
116. Sheehy AM, Gaddis NC, Malim MH (2003) The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med 9:1404-1407
117. Alce TM, Popik W (2004) APOBEC3G is incorporated into virus-like particles by a direct interaction with HIV-1 Gag nucleocapsid protein. J Biol Chem 279:34083-34086
118. Bach D, Peddi S, Mangeat B, Lakkaraju A, Strub K, Trono D (2008) Characterization of APOBEC3G binding to 7SL RNA. Retrovirology 5:54
119. Bogerd HP, Cullen BR (2008) Single-stranded RNA facilitates nucleocapsid: aPOBEC3G complex formation. RNA 14:1228-1236
120. Burnett A, Spearman P (2007) APOBEC3G multimers are recruited to the plasma membrane for packaging into human immunodeficiency virus type 1 virus-like particles in an RNA-dependent process requiring the NC basic linker. J Virol 81:5000-5013
121. Cen S, Guo F, Niu M, Saadatmand J, Deflassieux J, Kleiman L (2004) The interaction between HIV-1 Gag and APOBEC3G. J Biol Chem 279:33177-33184
122. Douaisi M, Dussart S, Courcoul M, Bessou G, Vigne R, Decroly E (2004) HIV-1 and MLV Gag proteins are sufficient to recruit APOBEC3G into virus-like particles. Biochem Biophys Res Commun 321:566-573
123. Khan MA et al (2005) Viral RNA is required for the association of APOBEC3G with human immunodeficiency virus type 1 nucleoprotein complexes. J Virol 79:5870-5874
124. Luo K, Liu B, Xiao Z, Yu Y, Yu X, Gorelick R, Yu XF (2004) Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging. J Virol 78:11841-11852
125. Schafer A, Bogerd HP, Cullen BR (2004) Specific packaging of APOBEC3G into HIV-1 virions is mediated by the nucleocapsid domain of the gag polyprotein precursor. Virology 328:163-168
126. Strebel K, Khan MA (2008) APOBEC3G encapsidation into HIV-1 virions: which RNA is it? Retrovirology 5:55
127. Svarovskaia ES et al (2004) Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is incorporated into HIV-1 virions through interactions with viral and nonviral RNAs. J Biol Chem 279:35822-35828
128. Hache G, Liddament MT, Harris RS (2005) The retroviral hypermutation specificity of APOBEC3F and APOBEC3G is governed by the C-terminal DNA cytosine deaminase domain. J Biol Chem 280:10920-10924
129. Iwatani Y, Takeuchi H, Strebel K, Levin JG (2006) Biochemical activities of highly purified, catalytically active human APOBEC3G: correlation with antiviral effect. J Virol 80:5992-6002
130. Navarro F, Bollman B, Chen H, Konig R, Yu Q, Chiles K, Landau NR (2005) Complementary function of the two catalytic domains of APOBEC3G. Virology 333:374-386
131. Suspene R et al (2004) APOBEC3G is a single-stranded DNA cytidine deaminase and functions independently of HIV reverse transcriptase. Nucleic Acids Res 32:2421-2429
132. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99-103
133. Yu Q et al (2004) Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome. Nat Struct Mol Biol 11:435-442
134. Lecossier D, Bouchonnet F, Clavel F, Hance AJ (2003) Hypermutation of HIV-1 DNA in the absence of the VIF protein. Science 300:1112
135. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94-98
136. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113:803-809
137. Yang B, Chen K, Zhang C, Huang S, Zhang H (2007) Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. J Biol Chem 282:11667-11675
138. Kaiser SM, Emerman M (2006) Uracil DNA glycosylase is dispensable for human immunodeficiency virus type 1 replication and does not contribute to the antiviral effects of the cytidine deaminase Apobec3G. J Virol 80:875-882
139. Langlois MA, Neuberger MS (2008) Human APOBEC3G can restrict retroviral infection in avian cells and acts independently of both UNG and SMUG1. J Virol 82:4660-4664
140. Guenzel CA, Herate C, Le Rouzic E, Maidou-Peindara P, Sadler HA, Rouyez MC, Mansky LM, Benichou S (2012) Recruitment of the nuclear form of uracil DNA glycosylase into virus particles participates in the full infectivity of HIV-1. J Virol 86:2533-2544
141. Li XY, Guo F, Zhang L, Kleiman L, Cen S (2007) APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem 282:32065-32074
142. Iwatani Y et al (2007) Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res 35:7096-7108
143. Browne EP, Allers C, Landau NR (2009) Restriction of HIV-1 by APOBEC3G is cytidine deaminase-dependent. Virology 387:313-321
144. Miyagi E, Opi S, Takeuchi H, Khan M, Goila-Gaur R, Kao S, Strebel K (2007) Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1. J Virol 81:13346-13353
145. Schumacher AJ, Hache G, Macduff DA, Brown WL, Harris RS (2008) The DNA deaminase activity of human APOBEC3G is required for Ty1, MusD and HIV-1 restriction. J Virol 82(6):2652-2660
146. Ding Q et al (2011) APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. J Clin Invest 121:4526-4536
147. Nik-Zainal S et al (2012) The life history of 21 breast cancers. Cell 149:994-1007
148. Harris RS, Liddament MT (2004) Retroviral restriction by APOBEC proteins. Nat Rev Immunol 4:868-877
149. Pham P, Bransteitter R, Goodman MF (2005) Reward versus risk: DNA cytidine deaminases triggering immunity and disease. Biochemistry 44:2703-2715
150. Holden LG et al (2008) Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature 456:121-124
151. Prochnow C, Bransteitter R, Klein MG, Goodman MF, Chen XS (2007) The APOBEC-2 crystal structure and functional implications for the deaminase AID. Nature 445:447-451
152. Shandilya SM et al (2010) Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure 18:28-38
153. Kitamura S et al (2012) The APOBEC3C crystal structure and the interface for HIV-1 Vif binding. Nat Struct Mol Biol 19:1005-1010
154. Chen KM, Harjes E, Gross PJ, Fahmy A, Lu Y, Shindo K, Harris RS, Matsuo H (2008) Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature 452:116-119
155. Furukawa A et al (2009) Structure, interaction and real-time monitoring
156. Harjes E et al (2009) An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model. J Mol Biol 389:819-832
157. Bransteitter R, Prochnow C, Chen XS (2009) The current structural and functional understanding of APOBEC deaminases. Cell Mol Life Sci 66:3137-3147
158. Autore F, Bergeron JR, Malim MH, Fraternali F, Huthoff H (2010) Rationalisation of the differences between APOBEC3G structures from crystallography and NMR studies by molecular dynamics simulations. PLoS One 5:e11515
159. Chelico L, Pham P, Goodman MF (2009) Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. Philos Trans R Soc Lond B 364:583-593
160. Conticello SG (2008) The AID/APOBEC family of nucleic acid mutators. Genome Biol 9:229
161. Dickerson SK, Market E, Besmer E, Papavasiliou FN (2003) AID mediates hypermutation by deaminating single stranded DNA. J Exp Med 197:1291-1296
162. Chen KM, Martemyanova N, Lu Y, Shindo K, Matsuo H, Harris RS (2007) Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G. FEBS Lett 581:4761-4766
163. Kohli RM, Abrams SR, Gajula KS, Maul RW, Gearhart PJ, Stivers JT (2009) A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. J Biol Chem 284:22898-22904
164. Kohli RM et al (2010) Local sequence targeting in the AID/APOBEC family differentially impacts retroviral restriction and antibody diversification. J Biol Chem 285:40956-40964
165. Wang M, Rada C, Neuberger MS (2010) Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID. J Exp Med 207:141-153
166. Iwatani Y, Rosen AE, Guo J, Musier-Forsyth K, Levin JG (2003) Efficient initiation of HIV-1 reverse transcription in vitro. Requirement for RNA sequences downstream of the primer binding site abrogated by nucleocapsid protein-dependent primer-template interactions. J Biol Chem 278:14185-14195
167. Brar SS, Sacho EJ, Tessmer I, Croteau DL, Erie DA, Diaz M (2008) Activation-induced deaminase, AID, is catalytically active as a monomer on single-stranded DNA. DNA Repair (Amst) 7:77-87
168. Ta VT et al (2003) AID mutant analyses indicate requirement for class-switch-specific cofactors. Nat Immunol 4:843-848
169. Feng Y, Chelico L (2011) Intensity of deoxycytidine deamination of HIV-1 proviral DNA by the retroviral restriction factor APOBEC3G is mediated by the noncatalytic domain. J Biol Chem 286:11415-11426
170. Shlyakhtenko LS, Lushnikov AY, Miyagi A, Li M, Harris RS, Lyubchenko YL (2012) Nanoscale structure and dynamics of ABOBEC3G complexes with single-stranded DNA. Biochemistry 51:6432-6440
171. Lindahl T, Barnes DE (2000) Repair of endogenous DNA damage. Cold Spring Harb Symp Quant Biol 65:127-133
172. Nowarski R, Britan-Rosich E, Shiloach T, Kotler M (2008) Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase. Nat Struct Mol Biol 15:1059-1066
173. Halford SE, Marko JF (2004) How do site-specific DNA-binding proteins find their targets? Nucleic Acids Res 32:3040-3052
174. Gorman J, Greene EC (2008) Visualizing one-dimensional diffusion of proteins along DNA. Nat Struct Mol Biol 15:768-774
175. Kad NM, Wang H, Kennedy GG, Warshaw DM, Van Houten B (2010) Collaborative dynamic DNA scanning by nucleotide excision repair proteins investigated by single-molecule imaging of quantum-dot-labeled proteins. Mol Cell 37:702-713
176. Senavirathne G, Jaszczur M, Auerbach PA, Upton TG, Chelico L, Goodman MF, Rueda D (2012) Single-stranded DNA scanning and deamination by APOBEC3G cytidine deaminase at single-molecule resolution. J Biol Chem 287:15826-15835
177. Lee WI, Torgerson TR, Schumacher MJ, Yel L, Zhu Q, Ochs HD (2005) Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome. Blood 105:1881-1890
178. Razanajaona D et al (1996) Somatic mutations in human Ig variable genes correlate with a partially functional CD40-ligand in the X-linked hyper-IgM syndrome. J Immunol 157:1492-1498
179. Aruffo A et al (1993) The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell 72:291-300
180. DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G (1993) CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature 361:541-543
181. Korthauer U et al (1993) Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature 361:539-541
182. Fuleihan R, Ramesh N, Geha RS (1993) Role of CD40-CD40-ligand interaction in Ig-isotype switching. Curr Opin Immunol 5:963-967
183. Durandy A, Peron S, Taubenheim N, Fischer A (2006) Activation-induced cytidine deaminase: structure-function relationship as based on the study of mutants. Hum Mutat 27:1185-1191
184. Durandy A, Taubenheim N, Peron S, Fischer A (2007) Pathophysiology of B cell intrinsic immunoglobulin class switch recombination deficiencies. Adv Immunol 94:275-306
185. Kracker S, Durandy A (2011) Insights into the B cell specific process of immunoglobulin class switch recombination. Immunol Lett 138:97-103
186. Minegishi Y et al (2000) Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome. Clin Immunol 97:203-210
187. Zhu Y, Nonoyama S, Morio T, Muramatsu M, Honjo T, Mizutani S (2003) Type two hyper-IgM syndrome caused by mutation in activation-induced cytidine deaminase. J Med Dent Sci 50:41-46
188. Imai K, Zhu Y, Revy P, Morio T, Mizutani S, Fischer A, Nonoyama S, Durandy A (2005) Analysis of class switch recombination and somatic hypermutation in patients affected with autosomal dominant hyper-IgM syndrome type 2. Clin Immunol 115:277-285
189. Barreto V, Reina-San-Martin B, Ramiro AR, McBride KM, Nussenzweig MC (2003) C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion. Mol Cell 12:501-508
190. Wang M, Yang Z, Rada C, Neuberger MS (2009) AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity. Nat Struct Mol Biol 16:769-776
191. Bransteitter R, Pham P, Calabrese P, Goodman MF (2004) Biochemical analysis of hypermutational targeting by wild type and mutant activation-induced cytidine deaminase. J Biol Chem 279:51612-51621
192. Suspene R, Rusniok C, Vartanian JP, Wain-Hobson S (2006) Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral replication. Nucleic Acids Res 34:4677-4684
193. Beale RC, Petersen-Mahrt SK, Watt IN, Harris RS, Rada C, Neuberger MS (2004) Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo. J Mol Biol 337:585-596
194. Bransteitter R, Pham P, Scharff MD, Goodman MF (2003) Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci USA 100:4102-4107
195. Shen HM, Poirier MG, Allen MJ, North J, Lal R, Widom J, Storb U (2009) The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription. J Exp Med 206:1057-1071
196. Storb U, Shen HM, Nicolae D (2009) Somatic hypermutation: processivity of the cytosine deaminase AID and error-free repair of the resulting uracils. Cell Cycle 8:3097-3101
197. Zaheen A, Boulianne B, Parsa JY, Ramachandran S, Gommerman JL, Martin A (2009) AID constrains germinal center size by rendering B cells susceptible to apoptosis. Blood 114:547-554
198. Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA (1996) A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 384:87-92
199. Bruner SD, Norman DP, Verdine GL (2000) Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403:859-866
200. Canugovi C, Samaranayake M, Bhagwat AS (2009) Transcriptional pausing and stalling causes multiple clustered mutations by human activation-induced deaminase. FASEB J 23:34-44
201. van Oijen AM (2011) Single-molecule approaches to characterizing kinetics of biomolecular interactions. Curr Opin Biotechnol 22:75-80
202. Myong S, Ha T (2010) Stepwise translocation of nucleic acid motors. Curr Opin Struct Biol 20:121-127
203. Roy R, Hohng S, Ha T (2008) A practical guide to single-molecule FRET. Nat Methods 5:507-516
204. McKinney SA, Joo C, Ha T (2006) Analysis of single-molecule FRET trajectories using hidden Markov modeling. Biophys J 91:1941-1951
205. Lasken RS, Schuster DM, Rashtchian A (1996) Archaebacterial DNA polymerases tightly bind uracil-containing DNA. J Biol Chem 271:17692-17696
206. Fogg MJ, Pearl LH, Connolly BA (2002) Structural basis for uracil recognition by archaeal family B DNA polymerases. Nat Struct Biol 9:922-927
207. Feng S, Jacobsen SE, Reik W (2010) Epigenetic reprogramming in plant and animal development. Science 330:622-627
208. Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11:204-220
209. Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279:52353-52360
210. Larijani M, Frieder D, Sonbuchner TM, Bransteitter R, Goodman MF, Bouhassira EE, Scharff MD, Martin A (2005) Methylation protects cytidines from AID-mediated deamination. Mol Immunol 42:599-604
211. Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008) DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135:1201-1212
212. Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, Jacobsen SE, Reik W (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463:1101-1105
213. Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463:1042-1047
214. Chahwan R, Wontakal SN, Roa S (2010) Crosstalk between genetic and epigenetic information through cytosine deamination. Trends Genet 26:443-448