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Generation of Genomic Alteration from Cytidine Deamination

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Chromosome Translocation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1044))

Abstract

The sources of genome instability can be attributed to many extra- and exo- cellular factors accompanying various biological processes. In leukemia and lymphomas, the collateral effect of programmed DNA alterations during immune diversification is the major source of genome instability. Cytidine deamination from cytidine (C) to uridine (U) at immunoglobulin (Ig) gene loci is required for initiation of antibody diversification, while the same process also contributes to recurrent translocation or mutations outside of Ig loci in lymphocyte-origin tumors. Furthermore, genome sequencing of cancer cells from many tissue origins revealed a significant enrichment of cytidine deaminase mutagenesis signature in human cancers. Thus, cytidine deamination, which can intensively happen in an enzyme-dependent fashion at specific genomic regions, is a widespread genome instability source across many tumor types. AID/APOBEC superfamily proteins are the main single-stranded DNA deaminases in eukaryotes, which play vital roles in adaptive and innate immunity. Their deamination products can be channeled into mutations, insertions and deletions (indels), clusters of mutations called kaetagis, or chromosomal rearrangements/translocations. Here, we review the generation of genome instability from AID/APOBEC-dependent cytidine deamination with emphasis on the most studied enzyme, AID.

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References

  1. Alt FW, Zhang Y, Meng FL, Guo C, Schwer B (2013) Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell 152(3):417–429. https://doi.org/10.1016/j.cell.2013.01.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Aoufouchi S, Faili A, Zober C, D'Orlando O, Weller S, Weill JC, Reynaud CA (2008) Proteasomal degradation restricts the nuclear lifespan of AID. J Exp Med 205(6):1357–1368. https://doi.org/10.1084/jem.20070950

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. 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(2):501–508

    Article  PubMed  CAS  Google Scholar 

  4. Basu U, Chaudhuri J, Alpert C, Dutt S, Ranganath S, Li G, Schrum JP, Manis JP, Alt FW (2005) The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature 438(7067):508–511. https://doi.org/10.1038/nature04255

    Article  PubMed  CAS  Google Scholar 

  5. Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW (2011) The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144(3):353–363. https://doi.org/10.1016/j.cell.2011.01.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Basu U, Wang Y, Alt FW (2008) Evolution of phosphorylation-dependent regulation of activation-induced cytidine deaminase. Mol Cell 32(2):285–291. https://doi.org/10.1016/j.molcel.2008.08.019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, Black DL, Smale ST (2012) Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 150(2):279–290. https://doi.org/10.1016/j.cell.2012.05.043

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY, Blau HM (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463(7284):1042–1047. https://doi.org/10.1038/nature08752

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Bishop KN, Holmes RK, Sheehy AM, Davidson NO, Cho SJ, Malim MH (2004) Cytidine deamination of retroviral DNA by diverse APOBEC proteins. Current biology : CB 14(15):1392–1396. https://doi.org/10.1016/j.cub.2004.06.057

    Article  PubMed  CAS  Google Scholar 

  10. Bogerd HP, Wiegand HL, Doehle BP, Lueders KK, Cullen BR (2006a) APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells. Nucleic Acids Res 34(1):89–95. https://doi.org/10.1093/nar/gkj416

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Bogerd HP, Wiegand HL, Hulme AE, Garcia-Perez JL, O'Shea KS, Moran JV, Cullen BR (2006b) Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. Proc Natl Acad Sci U S A 103(23):8780–8785. https://doi.org/10.1073/pnas.0603313103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 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 U S A 100(7):4102–4107. https://doi.org/10.1073/pnas.0730835100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, Refsland EW, Kotandeniya D, Tretyakova N, Nikas JB, Yee D, Temiz NA, Donohue DE, McDougle RM, Brown WL, Law EK, Harris RS (2013a) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494(7437):366–370. https://doi.org/10.1038/nature11881

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Burns MB, Temiz NA, Harris RS (2013b) Evidence for APOBEC3B mutagenesis in multiple human cancers. Nat Genet 45(9):977–983. https://doi.org/10.1038/ng.2701

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Cascalho M, Wong J, Steinberg C, Wabl M (1998) Mismatch repair co-opted by hypermutation. Science 279(5354):1207–1210

    Article  PubMed  CAS  Google Scholar 

  16. Chatterji M, Unniraman S, McBride KM, Schatz DG (2007) Role of activation-induced deaminase protein kinase A phosphorylation sites in Ig gene conversion and somatic hypermutation. J Immunol 179(8):5274–5280

    Article  PubMed  CAS  Google Scholar 

  17. Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, Perlot T, Vuong B, Wang J, Phan RT, Datta A, Manis J, Alt FW (2007) Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv Immunol 94:157–214. https://doi.org/10.1016/S0065-2776(06)94006-1

    Article  PubMed  CAS  Google Scholar 

  18. Chaudhuri J, Khuong C, Alt FW (2004) Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 430(7003):992–998. https://doi.org/10.1038/nature02821

    Article  PubMed  CAS  Google Scholar 

  19. 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(6933):726–730. https://doi.org/10.1038/nature01574

    Article  PubMed  CAS  Google Scholar 

  20. Cheng HL, Vuong BQ, Basu U, Franklin A, Schwer B, Astarita J, Phan RT, Datta A, Manis J, Alt FW, Chaudhuri J (2009) Integrity of the AID serine-38 phosphorylation site is critical for class switch recombination and somatic hypermutation in mice. Proc Natl Acad Sci U S A 106(8):2717–2722. https://doi.org/10.1073/pnas.0812304106

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho YJ, Myers DR, Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M, Alt FW (2011) Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147(1):107–119. https://doi.org/10.1016/j.cell.2011.07.049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Compagno M, Wang Q, Pighi C, Cheong TC, Meng FL, Poggio T, Yeap LS, Karaca E, Blasco RB, Langellotto F, Ambrogio C, Voena C, Wiestner A, Kasar SN, Brown JR, Sun J, Wu CJ, Gostissa M, Alt FW, Chiarle R (2017) Phosphatidylinositol 3-kinase delta blockade increases genomic instability in B cells. Nature 542(7642):489–493. https://doi.org/10.1038/nature21406

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Conticello SG (2008) The AID/APOBEC family of nucleic acid mutators. Genome Biol 9(6):229. https://doi.org/10.1186/gb-2008-9-6-229

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Core LJ, Waterfall JJ, Lis JT (2008) Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322(5909):1845–1848. https://doi.org/10.1126/science.1162228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Crouch EE, Li Z, Takizawa M, Fichtner-Feigl S, Gourzi P, Montano C, Feigenbaum L, Wilson P, Janz S, Papavasiliou FN, Casellas R (2007) Regulation of AID expression in the immune response. J Exp Med 204(5):1145–1156. https://doi.org/10.1084/jem.20061952

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, Muller H, Ragoussis J, Wei CL, Natoli G (2010) A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol 8(5):e1000384. https://doi.org/10.1371/journal.pbio.1000384

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Delker RK, Zhou Y, Strikoudis A, Stebbins CE, Papavasiliou FN (2013) Solubility-based genetic screen identifies RING finger protein 126 as an E3 ligase for activation-induced cytidine deaminase. Proc Natl Acad Sci U S A 110(3):1029–1034. https://doi.org/10.1073/pnas.1214538110

    Article  PubMed  Google Scholar 

  28. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146(6):904–917. https://doi.org/10.1016/j.cell.2011.08.017

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Di Noia JM, Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 76:1–22. https://doi.org/10.1146/annurev.biochem.76.061705.090740

    Article  PubMed  CAS  Google Scholar 

  30. Doehle BP, Schafer A, Cullen BR (2005) Human APOBEC3B is a potent inhibitor of HIV-1 infectivity and is resistant to HIV-1 Vif. Virology 339(2):281–288. https://doi.org/10.1016/j.virol.2005.06.005

    Article  CAS  PubMed  Google Scholar 

  31. Ehrenstein MR, Neuberger MS (1999) Deficiency in Msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination: parallels with somatic hypermutation. EMBO J 18(12):3484–3490. https://doi.org/10.1093/emboj/18.12.3484

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Ellyard JI, Benk AS, Taylor B, Rada C, Neuberger MS (2011) The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin. Eur J Immunol 41(2):485–490. https://doi.org/10.1002/eji.201041011

    Article  CAS  PubMed  Google Scholar 

  33. Fukita Y, Jacobs H, Rajewsky K (1998) Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 9(1):105–114

    Article  CAS  PubMed  Google Scholar 

  34. 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 U S A 106(16):6736–6741. https://doi.org/10.1073/pnas.0810808106

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gonda H, Sugai M, Nambu Y, Katakai T, Agata Y, Mori KJ, Yokota Y, Shimizu A (2003) The balance between Pax5 and Id2 activities is the key to AID gene expression. J Exp Med 198(9):1427–1437. https://doi.org/10.1084/jem.20030802

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. 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 U S A 100(7):4126–4131. https://doi.org/10.1073/pnas.0735266100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Hackney JA, Misaghi S, Senger K, Garris C, Sun Y, Lorenzo MN, Zarrin AA (2009) DNA targets of AID evolutionary link between antibody somatic hypermutation and class switch recombination. Adv Immunol 101:163–189. https://doi.org/10.1016/S0065-2776(08)01005-5

    Article  PubMed  CAS  Google Scholar 

  38. Han L, Mao W, Yu K (2012) X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining. Proc Natl Acad Sci U S A 109(12):4604–4608. https://doi.org/10.1073/pnas.1120743109

    Article  PubMed  PubMed Central  Google Scholar 

  39. Han L, Masani S, Yu K (2011) Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination. Proc Natl Acad Sci U S A 108(28):11584–11589. https://doi.org/10.1073/pnas.1018726108

    Article  PubMed  PubMed Central  Google Scholar 

  40. Haradhvala NJ, Polak P, Stojanov P, Covington KR, Shinbrot E, Hess JM, Rheinbay E, Kim J, Maruvka YE, Braunstein LZ, Kamburov A, Hanawalt PC, Wheeler DA, Koren A, Lawrence MS, Getz G (2016) Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. Cell 164(3):538–549. https://doi.org/10.1016/j.cell.2015.12.050

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. 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(6):803–809

    Article  PubMed  CAS  Google Scholar 

  42. Harris RS, Liddament MT (2004) Retroviral restriction by APOBEC proteins. Nature reviews Immunology 4(11):868–877. https://doi.org/10.1038/nri1489

    Article  PubMed  CAS  Google Scholar 

  43. Harris RS, Petersen-Mahrt SK, Neuberger MS (2002) RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell 10(5):1247–1253

    Article  PubMed  CAS  Google Scholar 

  44. Hasler J, Rada C, Neuberger MS (2011) Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1alpha (eEF1A). Proc Natl Acad Sci U S A 108(45):18366–18371. https://doi.org/10.1073/pnas.1106729108

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA (2013) Super-enhancers in the control of cell identity and disease. Cell 155(4):934–947. https://doi.org/10.1016/j.cell.2013.09.053

    Article  PubMed  CAS  Google Scholar 

  46. Honjo T, Kinoshita K, Muramatsu M (2002) Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annu Rev Immunol 20:165–196. https://doi.org/10.1146/annurev.immunol.20.090501.112049

    Article  PubMed  CAS  Google Scholar 

  47. Hoopes J, Cortez L, Mertz T, Malc EP, Mieczkowski PA, Roberts SA (2016) APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication. Cell Reports 14(6):1273–1282. https://doi.org/10.1016/j.celrep.2016.01.021

    Article  PubMed  CAS  Google Scholar 

  48. 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(3):277–285. https://doi.org/10.1016/j.clim.2005.02.003

    Article  CAS  PubMed  Google Scholar 

  49. Ise W, Kohyama M, Schraml BU, Zhang T, Schwer B, Basu U, Alt FW, Tang J, Oltz EM, Murphy TL, Murphy KM (2011) The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat Immunol 12(6):536–543. https://doi.org/10.1038/ni.2037

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, Navaratnam N (2002) An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 79(3):285–296. https://doi.org/10.1006/geno.2002.6718

    Article  PubMed  CAS  Google Scholar 

  51. Johnson DF, Poksay KS, Innerarity TL (1993) The mechanism for apo-B mRNA editing is deamination. Biochem Biophys Res Commun 195(3):1204–1210. https://doi.org/10.1006/bbrc.1993.2172

    Article  PubMed  CAS  Google Scholar 

  52. Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC (2011) Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 147(1):95–106. https://doi.org/10.1016/j.cell.2011.07.048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Kohli RM, Maul RW, Guminski AF, McClure RL, Gajula KS, Saribasak H, McMahon MA, Siliciano RF, Gearhart PJ, Stivers JT (2010) Local sequence targeting in the AID/APOBEC family differentially impacts retroviral restriction and antibody diversification. J Biol Chem 285(52):40956–40964. https://doi.org/10.1074/jbc.M110.177402

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533(7603):420–424. https://doi.org/10.1038/nature17946

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Kuong KJ, Loeb LA (2013) APOBEC3B mutagenesis in cancer. Nature Genet 45(9):964–965. https://doi.org/10.1038/ng.2736

    Article  PubMed  CAS  Google Scholar 

  56. Kuppers R, Dalla-Favera R (2001) Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20(40):5580–5594. https://doi.org/10.1038/sj.onc.1204640

    Article  PubMed  CAS  Google Scholar 

  57. Kuscu C, Adli M (2016) CRISPR-Cas9-AID base editor is a powerful gain-of-function screening tool. Nature methods 13(12):983–984. https://doi.org/10.1038/nmeth.4076

    Article  PubMed  CAS  Google Scholar 

  58. Kwak H, Fuda NJ, Core LJ, Lis JT (2013) Precise maps of RNA polymerase reveal how promoters direct initiation and pausing. Science 339(6122):950–953. https://doi.org/10.1126/science.1229386

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Leonard B, Hart SN, Burns MB, Carpenter MA, Temiz NA, Rathore A, Vogel RI, Nikas JB, Law EK, Brown WL, Li Y, Zhang Y, Maurer MJ, Oberg AL, Cunningham JM, Shridhar V, Bell DA, April C, Bentley D, Bibikova M, Cheetham RK, Fan JB, Grocock R, Humphray S, Kingsbury Z, Peden J, Chien J, Swisher EM, Hartmann LC, Kalli KR, Goode EL, Sicotte H, Kaufmann SH, Harris RS (2013) APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma. Cancer Res 73(24):7222–7231. https://doi.org/10.1158/0008-5472.CAN-13-1753

    Article  PubMed  CAS  Google Scholar 

  60. 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(7180):841–845. https://doi.org/10.1038/nature06547

    Article  PubMed  CAS  Google Scholar 

  61. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA (2013) Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153(2):320–334. https://doi.org/10.1016/j.cell.2013.03.036

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Huser N, Durantel D, Liang TJ, Munk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U (2014) Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science 343(6176):1221–1228. https://doi.org/10.1126/science.1243462

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  63. Lutzker S, Alt FW (1988) Structure and expression of germ line immunoglobulin gamma 2b transcripts. Mol Cell Biol 8(4):1849–1852

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. 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(2):177–184

    Article  PubMed  CAS  Google Scholar 

  65. Ma Y, Zhang J, Yin W, Zhang Z, Song Y, Chang X (2016) Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nature methods 13(12):1029–1035. https://doi.org/10.1038/nmeth.4027

    Article  PubMed  CAS  Google Scholar 

  66. Mahdaviani SA, Hirbod-Mobarakeh A, Wang N, Aghamohammadi A, Hammarstrom L, Masjedi MR, Pan-Hammarstrom Q, Rezaei N (2012) Novel mutation of the activation-induced cytidine deaminase gene in a Tajik family: special review on hyper-immunoglobulin M syndrome. Expert Rev Clin Immunol 8(6):539–546. https://doi.org/10.1586/eci.12.46

    Article  PubMed  CAS  Google Scholar 

  67. 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(6944):99–103. https://doi.org/10.1038/nature01709

    Article  PubMed  CAS  Google Scholar 

  68. Martin A, Li Z, Lin DP, Bardwell PD, Iglesias-Ussel MD, Edelmann W, Scharff MD (2003) Msh2 ATPase activity is essential for somatic hypermutation at a-T basepairs and for efficient class switch recombination. J Exp Med 198(8):1171–1178. https://doi.org/10.1084/jem.20030880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Marusawa H, Takai A, Chiba T (2011) Role of activation-induced cytidine deaminase in inflammation-associated cancer development. Adv Immunol 111:109–141. https://doi.org/10.1016/B978-0-12-385991-4.00003-9

    Article  PubMed  CAS  Google Scholar 

  70. McBride KM, Barreto V, Ramiro AR, Stavropoulos P, Nussenzweig MC (2004) Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J Exp Med 199(9):1235–1244. https://doi.org/10.1084/jem.20040373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. McBride KM, Gazumyan A, Woo EM, Barreto VM, Robbiani DF, Chait BT, Nussenzweig MC (2006) Regulation of hypermutation by activation-induced cytidine deaminase phosphorylation. Proc Natl Acad Sci U S A 103(23):8798–8803. https://doi.org/10.1073/pnas.0603272103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. 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(11):2585–2594. https://doi.org/10.1084/jem.20081319

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Meng FL, Du Z, Federation A, Hu J, Wang Q, Kieffer-Kwon KR, Meyers RM, Amor C, Wasserman CR, Neuberg D, Casellas R, Nussenzweig MC, Bradner JE, Liu XS, Alt FW (2014) Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell 159(7):1538–1548. https://doi.org/10.1016/j.cell.2014.11.014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Migliazza A, Martinotti S, Chen W, Fusco C, Ye BH, Knowles DM, Offit K, Chaganti RS, Dalla-Favera R (1995) Frequent somatic hypermutation of the 5′ noncoding region of the BCL6 gene in B-cell lymphoma. Proc Natl Acad Sci U S A 92(26):12520–12524

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. 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(5):553–563

    Article  PubMed  CAS  Google Scholar 

  76. 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(26):18470–18476

    Article  PubMed  CAS  Google Scholar 

  77. 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(12):1833–1840

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Nambu Y, Sugai M, Gonda H, Lee CG, Katakai T, Agata Y, Yokota Y, Shimizu A (2003) Transcription-coupled events associating with immunoglobulin switch region chromatin. Science 302(5653):2137–2140. https://doi.org/10.1126/science.1092481

    Article  PubMed  CAS  Google Scholar 

  79. Navaratnam N, Morrison JR, Bhattacharya S, Patel D, Funahashi T, Giannoni F, Teng BB, Davidson NO, Scott J (1993) The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. J Biol Chem 268(28):20709–20712

    PubMed  CAS  Google Scholar 

  80. Neuberger MS, Rada C (2007) Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase eta for A/T. J Exp Med 204(1):7–10. https://doi.org/10.1084/jem.20062409

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, Jones D, Hinton J, Marshall J, Stebbings LA, Menzies A, Martin S, Leung K, Chen L, Leroy C, Ramakrishna M, Rance R, Lau KW, Mudie LJ, Varela I, DJ MB, Bignell GR, Cooke SL, Shlien A, Gamble J, Whitmore I, Maddison M, Tarpey PS, Davies HR, Papaemmanuil E, Stephens PJ, McLaren S, Butler AP, Teague JW, Jonsson G, Garber JE, Silver D, Miron P, Fatima A, Boyault S, Langerod A, Tutt A, Martens JW, Aparicio SA, Borg A, Salomon AV, Thomas G, Borresen-Dale AL, Richardson AL, Neuberger MS, Futreal PA, Campbell PJ, Stratton MR, Breast Cancer Working Group of the International Cancer Genome C (2012) Mutational processes molding the genomes of 21 breast cancers. Cell 149(5):979–993. https://doi.org/10.1016/j.cell.2012.04.024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Nik-Zainal S, Wedge DC, Alexandrov LB, Petljak M, Butler AP, Bolli N, Davies HR, Knappskog S, Martin S, Papaemmanuil E, Ramakrishna M, Shlien A, Simonic I, Xue Y, Tyler-Smith C, Campbell PJ, Stratton MR (2014) Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer. Nature Genet 46(5):487–491. https://doi.org/10.1038/ng.2955

    Article  PubMed  CAS  Google Scholar 

  83. Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M, Mochizuki M, Miyabe A, Araki M, Hara KY, Shimatani Z, Kondo A (2016) Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353(6305). https://doi.org/10.1126/science.aaf8729

    Article  PubMed  CAS  Google Scholar 

  84. Noguchi C, Ishino H, Tsuge M, Fujimoto Y, Imamura M, Takahashi S, Chayama K (2005) G to A hypermutation of hepatitis B virus. Hepatology 41(3):626–633. https://doi.org/10.1002/hep.20580

    Article  PubMed  CAS  Google Scholar 

  85. Nowak U, Matthews AJ, Zheng S, Chaudhuri J (2011) The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nat Immunol 12(2):160–166. https://doi.org/10.1038/ni.1977

    Article  PubMed  CAS  Google Scholar 

  86. Ohm-Laursen L, Barington T (2007) Analysis of 6912 unselected somatic hypermutations in human VDJ rearrangements reveals lack of strand specificity and correlation between phase II substitution rates and distance to the nearest 3′ activation-induced cytidine deaminase target. J Immunol 178(7):4322–4334

    Article  PubMed  Google Scholar 

  87. Omori SA, Cato MH, Anzelon-Mills A, Puri KD, Shapiro-Shelef M, Calame K, Rickert RC (2006) Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity 25(4):545–557. https://doi.org/10.1016/j.immuni.2006.08.015

    Article  PubMed  CAS  Google Scholar 

  88. Orthwein A, Patenaude AM, Affar el B, Lamarre A, Young JC, Di Noia JM (2010) Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90. J Exp Med 207(12):2751–2765. https://doi.org/10.1084/jem.20101321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Pasqualucci L, Migliazza A, Fracchiolla N, William C, Neri A, Baldini L, Chaganti RS, Klein U, Kuppers R, Rajewsky K, Dalla-Favera R (1998) BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci U S A 95(20):11816–11821

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, Dalla-Favera R (2001) Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 412(6844):341–346. https://doi.org/10.1038/35085588

    Article  PubMed  CAS  Google Scholar 

  91. 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 TJ, Root DE, Casellas R, Nussenzweig MC (2010) Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 143(1):122–133. https://doi.org/10.1016/j.cell.2010.09.017

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Pefanis E, Wang J, Rothschild G, Lim J, Chao J, Rabadan R, Economides AN, Basu U (2014) Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature. https://doi.org/10.1038/nature13580

  93. Pefanis E, Wang J, Rothschild G, Lim J, Kazadi D, Sun J, Federation A, Chao J, Elliott O, Liu ZP, Economides AN, Bradner JE, Rabadan R, Basu U (2015) RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161(4):774–789. https://doi.org/10.1016/j.cell.2015.04.034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Petersen-Mahrt SK, Harris RS, Neuberger MS (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418(6893):99–103. https://doi.org/10.1038/nature00862

    Article  PubMed  CAS  Google Scholar 

  95. Petersen-Mahrt SK, Neuberger MS (2003) In vitro deamination of cytosine to uracil in single-stranded DNA by apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). J Biol Chem 278(22):19583–19586. https://doi.org/10.1074/jbc.C300114200

    Article  PubMed  CAS  Google Scholar 

  96. Pham P, Bransteitter R, Petruska J, Goodman MF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424(6944):103–107. https://doi.org/10.1038/nature01760

    Article  PubMed  CAS  Google Scholar 

  97. Pham P, Smolka MB, Calabrese P, Landolph A, Zhang K, Zhou H, Goodman MF (2008) Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase. J Biol Chem 283(25):17428–17439. https://doi.org/10.1074/jbc.M802121200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. 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(7284):1101–1105. https://doi.org/10.1038/nature08829

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. 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(7126):447–451. https://doi.org/10.1038/nature05492

    Article  PubMed  CAS  Google Scholar 

  100. Qian J, Wang Q, Dose M, Pruett N, Kieffer-Kwon KR, Resch W, Liang G, Tang Z, Mathe E, Benner C, Dubois W, Nelson S, Vian L, Oliveira TY, Jankovic M, Hakim O, Gazumyan A, Pavri R, Awasthi P, Song B, Liu G, Chen L, Zhu S, Feigenbaum L, Staudt L, Murre C, Ruan Y, Robbiani DF, Pan-Hammarstrom Q, Nussenzweig MC, Casellas R (2014) B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity. Cell 159(7):1524–1537. https://doi.org/10.1016/j.cell.2014.11.013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Qiao Q, Wang L, Meng FL, Hwang JK, Alt FW, Wu H (2017) AID Recognizes Structured DNA for Class Switch Recombination. Molecular cell 67(3):361–373. e364. https://doi.org/10.1016/j.molcel.2017.06.034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Quinlan EM, King JJ, Amemiya CT, Hsu E, Larijani M (2017) Biochemical regulatory features of AID remain conserved from lamprey to humans. Mol Cell Biol. https://doi.org/10.1128/MCB.00077-17

  103. 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(2):163–171. https://doi.org/10.1016/j.molcel.2004.10.011

    Article  PubMed  CAS  Google Scholar 

  104. 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(5):2464–2475. https://doi.org/10.4049/jimmunol.1101406

    Article  PubMed  CAS  Google Scholar 

  105. Rathore A, Carpenter MA, Demir O, Ikeda T, Li M, Shaban NM, Law EK, Anokhin D, Brown WL, Amaro RE, Harris RS (2013) The local dinucleotide preference of APOBEC3G can be altered from 5′-CC to 5′-TC by a single amino acid substitution. J Mol Biol 425(22):4442–4454. https://doi.org/10.1016/j.jmb.2013.07.040

    Article  PubMed  CAS  Google Scholar 

  106. 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, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102(5):565–575

    Article  PubMed  CAS  Google Scholar 

  107. Robbiani DF, Nussenzweig MC (2013) Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase. Annu Rev Pathol 8:79–103. https://doi.org/10.1146/annurev-pathol-020712-164004

    Article  PubMed  CAS  Google Scholar 

  108. Rogozin IB, Basu MK, Jordan IK, Pavlov YI, Koonin EV (2005) APOBEC4, a new member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases predicted by computational analysis. Cell cycle 4(9):1281–1285. https://doi.org/10.4161/cc.4.9.1994

    Article  PubMed  CAS  Google Scholar 

  109. Rogozin IB, Diaz M (2004) 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 172(6):3382–3384

    Article  PubMed  CAS  Google Scholar 

  110. Rosenberg BR, Hamilton CE, Mwangi MM, Dewell S, Papavasiliou FN (2011) Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3′ UTRs. Nat Struct Mol Biol 18 (2):230-236. https://doi.org/10.1038/nsmb.1975

    Article  CAS  Google Scholar 

  111. Rosler C, Kock J, Kann M, Malim MH, Blum HE, Baumert TF, von Weizsacker F (2005) APOBEC-mediated interference with hepadnavirus production. Hepatology 42(2):301–309. https://doi.org/10.1002/hep.20801

    Article  PubMed  CAS  Google Scholar 

  112. Rothman P, Chen YY, Lutzker S, Li SC, Stewart V, Coffman R, Alt FW (1990) Structure and expression of germ line immunoglobulin heavy-chain epsilon transcripts: interleukin-4 plus lipopolysaccharide-directed switching to C epsilon. Mol Cell Biol 10(4):1672–1679

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Rothman P, Lutzker S, Cook W, Coffman R, Alt FW (1988) Mitogen plus interleukin 4 induction of C epsilon transcripts in B lymphoid cells. J Exp Med 168(6):2385–2389

    Article  PubMed  CAS  Google Scholar 

  114. Salter JD, Bennett RP, Smith HC (2016) The APOBEC Protein Family: United by Structure, Divergent in Function. Trends Biochem Sci 41(7):578–594. https://doi.org/10.1016/j.tibs.2016.05.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Sayegh CE, Quong MW, Agata Y, Murre C (2003) E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat Immunol 4(6):586–593. https://doi.org/10.1038/ni923

    Article  PubMed  CAS  Google Scholar 

  116. Seplyarskiy VB, Soldatov RA, Popadin KY, Antonarakis SE, Bazykin GA, Nikolaev SI (2016) APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication. Genome Res 26(2):174–182. https://doi.org/10.1101/gr.197046.115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. 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(6898):646–650. https://doi.org/10.1038/nature00939

    Article  PubMed  CAS  Google Scholar 

  118. 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(5370):1750–1752

    Article  CAS  PubMed  Google Scholar 

  119. 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(8):5386–5392

    Article  PubMed  CAS  Google Scholar 

  120. Shi K, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy JV, Demir O, Amaro RE, Harki DA, Harris RS, Aihara H (2017) Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Nature Struct Mol Biol 24(2):131–139. https://doi.org/10.1038/nsmb.3344

    Article  CAS  Google Scholar 

  121. Shinkura R, Ito S, Begum NA, Nagaoka H, Muramatsu M, Kinoshita K, Sakakibara Y, Hijikata H, Honjo T (2004) Separate domains of AID are required for somatic hypermutation and class-switch recombination. Nat Immunol 5(7):707–712. https://doi.org/10.1038/ni1086

    Article  PubMed  CAS  Google Scholar 

  122. Shulman Z, Gitlin AD, Targ S, Jankovic M, Pasqual G, Nussenzweig MC, Victora GD (2013) T follicular helper cell dynamics in germinal centers. Science 341(6146):673–677. https://doi.org/10.1126/science.1241680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Stavnezer-Nordgren J, Sirlin S (1986) Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. EMBO J 5(1):95–102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Stavnezer J (1986) Presence of a polyadenylated RNA fragment encoding the membrane domain for immunoglobulin alpha chain indicates that mRNAs for both secreted and membrane-bound alpha chains can be produced from the same RNA transcript. Nucleic Acids Res 14(15):6129–6144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Stenglein MD, Harris RS (2006) APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism. J Biol Chem 281(25):16837–16841. https://doi.org/10.1074/jbc.M602367200

    Article  PubMed  CAS  Google Scholar 

  126. Suspene R, Guetard D, Henry M, Sommer P, Wain-Hobson S, Vartanian JP (2005) Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo. Proc Natl Acad Sci U S A 102(23):8321–8326. https://doi.org/10.1073/pnas.0408223102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Ta VT, Nagaoka H, Catalan N, Durandy A, Fischer A, Imai K, Nonoyama S, Tashiro J, Ikegawa M, Ito S, Kinoshita K, Muramatsu M, Honjo T (2003) AID mutant analyses indicate requirement for class-switch-specific cofactors. Nat Immunol 4(9):843–848. https://doi.org/10.1038/ni964

    Article  PubMed  CAS  Google Scholar 

  128. Takai A, Toyoshima T, Uemura M, Kitawaki Y, Marusawa H, Hiai H, Yamada S, Okazaki IM, Honjo T, Chiba T, Kinoshita K (2009) A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. Oncogene 28(4):469–478. https://doi.org/10.1038/onc.2008.415

    Article  PubMed  CAS  Google Scholar 

  129. Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, Raine K, Campbell PJ, Rada C, Stratton MR, Neuberger MS (2013) DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. eLife 2:e00534. https://doi.org/10.7554/eLife.00534

    Article  PubMed  PubMed Central  Google Scholar 

  130. Teng B, Burant CF, Davidson NO (1993) Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science 260(5115):1816–1819

    Article  PubMed  CAS  Google Scholar 

  131. Tran TH, Nakata M, Suzuki K, Begum NA, Shinkura R, Fagarasan S, Honjo T, Nagaoka H (2010) B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers. Nat Immunol 11(2):148–154. https://doi.org/10.1038/ni.1829

    Article  PubMed  CAS  Google Scholar 

  132. Turelli P, Trono D (2005) Editing at the crossroad of innate and adaptive immunity. Science 307(5712):1061–1065. https://doi.org/10.1126/science.1105964

    Article  PubMed  CAS  Google Scholar 

  133. Vartanian JP, Guetard D, Henry M, Wain-Hobson S (2008) Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions. Science 320(5873):230–233. https://doi.org/10.1126/science.1153201

    Article  PubMed  CAS  Google Scholar 

  134. Victora GD, Nussenzweig MC (2012) Germinal centers. Annu Rev Immunol 30:429–457. https://doi.org/10.1146/annurev-immunol-020711-075032

    Article  PubMed  CAS  Google Scholar 

  135. 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(4):420–426. https://doi.org/10.1038/ni.1708

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. 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(1):141–153. https://doi.org/10.1084/jem.20092238

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T (2011) Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat Immunol 12(3):264–270. https://doi.org/10.1038/ni.1991

    Article  PubMed  CAS  Google Scholar 

  138. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153(2):307–319. https://doi.org/10.1016/j.cell.2013.03.035

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Xu Z, Fulop Z, Wu G, Pone EJ, Zhang J, Mai T, Thomas LM, Al-Qahtani A, White CA, Park SR, Steinacker P, Li Z, Yates J 3rd, Herron B, Otto M, Zan H, Fu H, Casali P (2010) 14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′-rich switch regions for class switch recombination. Nat Struct Mol Biol 17(9):1124–1135. https://doi.org/10.1038/nsmb.1884

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. 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(9):2085–2094. https://doi.org/10.1084/jem.20061067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Yamane A, Resch W, Kuo N, Kuchen S, Li Z, Sun HW, Robbiani DF, McBride K, Nussenzweig MC, Casellas R (2011) Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nat Immunol 12(1):62–69. https://doi.org/10.1038/ni.1964

    Article  PubMed  CAS  Google Scholar 

  142. Yancopoulos GD, DePinho RA, Zimmerman KA, Lutzker SG, Rosenberg N, Alt FW (1986) Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching. EMBO J 5(12):3259–3266

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Yeap LS, Hwang JK, Du Z, Meyers RM, Meng FL, Jakubauskaite A, Liu M, Mani V, Neuberg D, Kepler TB, Wang JH, Alt FW (2015) Sequence-intrinsic mechanisms that target AID mutational outcomes on antibody genes. Cell 163(5):1124–1137

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Zahn A, Eranki AK, Patenaude AM, Methot SP, Fifield H, Cortizas EM, Foster P, Imai K, Durandy A, Larijani M, Verdun RE, Di Noia JM (2014) Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.1320486111

  145. 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(6944):94–98. https://doi.org/10.1038/nature01707

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Zhang Y, Gostissa M, Hildebrand DG, Becker MS, Boboila C, Chiarle R, Lewis S, Alt FW (2010) The role of mechanistic factors in promoting chromosomal translocations found in lymphoid and other cancers. Adv Immunol 106:93–133. https://doi.org/10.1016/S0065-2776(10)06004-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Zheng S, Vuong BQ, Vaidyanathan B, Lin JY, Huang FT, Chaudhuri J (2015) Non-coding RNA generated following Lariat Debranching mediates targeting of AID to DNA. Cell 161(4):762–773. https://doi.org/10.1016/j.cell.2015.03.020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

Research in the authors’ lab is supported by grants from Science and Technology Commission of Shanghai Municipality (16ZR1441600), National Natural Science Foundation of China (8162200437, 31670929).

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    Xiaojing Liu & Fei-Long Meng

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Liu, X., Meng, FL. (2018). Generation of Genomic Alteration from Cytidine Deamination. In: Zhang, Y. (eds) Chromosome Translocation. Advances in Experimental Medicine and Biology, vol 1044. Springer, Singapore. https://doi.org/10.1007/978-981-13-0593-1_5

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