Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases

Chemical Reviews

Volumn 116, Issue 20, 2016, Pages 12688-12710

  Siriwardena, Sachini U ^a   Chen, Kang ^b,c   Bhagwat, Ashok S ^a,b  

^a WAYNE STATE UNIVERSITY   (United States)

^b WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODIES; DNA; ENZYMES; MAMMALS; TRANSCRIPTION; VIRUSES;

CELLULAR GENOMES; CYTOSINE DEAMINASES; INFLAMMATORY RESPONSE; PHYSIOLOGICAL STATE; REPLICATION FORK; RETROTRANSPOSITION; SINGLE-STRANDED DNA; SOMATIC HYPERMUTATION;

NUCLEIC ACIDS;

AICDA (ACTIVATION-INDUCED CYTIDINE DEAMINASE); APOLIPOPROTEIN B MRNA EDITING ENZYME CATALYTIC POLYPEPTIDE LIKE; CYTIDINE DEAMINASE; DNA;

ANIMAL; MAMMAL; METABOLISM;

ANIMALS; APOBEC DEAMINASES; CYTIDINE DEAMINASE; DNA; MAMMALS;

EID: 84993950015     PISSN: 00092665     EISSN: 15206890     Source Type: Journal    
DOI: 10.1021/acs.chemrev.6b00296     Document Type: Review

References (341)

1. Beale, R. C.; Petersen-Mahrt, S. K.; Watt, I. N.; Harris, R. S.; Rada, C.; Neuberger, M. S. Comparison of the Differential Context-Dependence of DNA Deamination by APOBEC Enzymes: Correlation with Mutation Spectra in Vivo J. Mol. Biol. 2004, 337, 585-596 10.1016/j.jmb.2004.01.046
2. Bransteitter, R.; Pham, P.; Scharff, M. D.; Goodman, M. F. Activation-Induced Cytidine Deaminase Deaminates Deoxycytidine on Single-Stranded DNA but Requires the Action of RNAse Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 4102-4107 10.1073/pnas.0730835100
3. 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 10.1038/nature01574
4. 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 10.1084/jem.20030481
5. Petersen-Mahrt, S. K.; Neuberger, M. S. In Vitro Deamination of Cytosine to Uracil in Single-Stranded DNA by Apolipoprotein B Editing Complex Catalytic Subunit 1 (APOBEC1) J. Biol. Chem. 2003, 278, 19583-19586 10.1074/jbc.C300114200
6. Sohail, A.; Klapacz, J.; Samaranayake, M.; Ullah, A.; Bhagwat, A. S. Human Activation-Induced Cytidine Deaminase Causes Transcription-Dependent, Strand-Biased C to U Deaminations Nucleic Acids Res. 2003, 31, 2990-2994 10.1093/nar/gkg464
7. Teng, B.; Burant, C. F.; Davidson, N. O. Molecular Cloning of an Apolipoprotein B Messenger RNA Editing Protein Science 1993, 260, 1816-1819 10.1126/science.8511591
8. Wijesinghe, P.; Bhagwat, A. S. Efficient Deamination of 5-Methylcytosines in DNA by Human APOBEC3A, but Not by AID or APOBEC3G Nucleic Acids Res. 2012, 40, 9206-9217 10.1093/nar/gks685
9. Sharma, S.; Patnaik, S. K.; Taggart, R. T.; Kannisto, E. D.; Enriquez, S. M.; Gollnick, P.; Baysal, B. E. APOBEC3A Cytidine Deaminase Induces RNA Editing in Monocytes and Macrophages Nat. Commun. 2015, 6, 6881 10.1038/ncomms7881
10. LaRue, R. S.; Andresdottir, V.; Blanchard, Y.; Conticello, S. G.; Derse, D.; Emerman, M.; Greene, W. C.; Jonsson, S. R.; Landau, N. R.; Lochelt, M. et al. Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins J. Virol. 2009, 83, 494-497 10.1128/JVI.01976-08
11. Conticello, S. G. The AID/APOBEC Family of Nucleic Acid Mutators Genome Biol. 2008, 9, 229 10.1186/gb-2008-9-6-229
12. Harris, R. S.; Petersen-Mahrt, S. K.; Neuberger, M. S. RNA Editing Enzyme APOBEC1 and Some of Its Homologs Can. Act as DNA Mutators Mol. Cell 2002, 10, 1247-1253 10.1016/S1097-2765(02)00742-6
13. Marino, D.; Perkovic, M.; Hain, A.; Jaguva Vasudevan, A. A.; Hofmann, H.; Hanschmann, K. M.; Muhlebach, M. D.; Schumann, G. G.; Konig, R.; Cichutek, K. et al. APOBEC4 Enhances the Replication of HIV-1 PLoS One 2016, 11, e0155422 10.1371/journal.pone.0155422
14. Neuberger, M. S.; Harris, R. S.; Di Noia, J.; Petersen-Mahrt, S. K. Immunity through DNA Deamination Trends Biochem. Sci. 2003, 28, 305-312 10.1016/S0968-0004(03)00111-7
15. Jarmuz, A.; Chester, A.; Bayliss, J.; Gisbourne, J.; Dunham, I.; Scott, J.; Navaratnam, N. An Anthropoid-Specific Locus of Orphan C to U RNA-Editing Enzymes on Chromosome 22 Genomics 2002, 79, 285-296 10.1006/geno.2002.6718
16. 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 10.1038/nature01760
17. Harris, R. S.; Liddament, M. T. Retroviral Restriction by APOBEC Proteins Nat. Rev. Immunol. 2004, 4, 868-877 10.1038/nri1489
18. Berg, O. G.; Winter, R. B.; von Hippel, P. H. Diffusion-Driven Mechanisms of Protein Translocation on Nucleic Acids. 1. Models and Theory Biochemistry 1981, 20, 6929-6948 10.1021/bi00527a028
19. Halford, S. E.; Marko, J. F. How Do Site-Specific DNA-Binding Proteins Find Their Targets? Nucleic Acids Res. 2004, 32, 3040-3052 10.1093/nar/gkh624
20. Redding, S.; Greene, E. C. How Do Proteins Locate Specific Targets in DNA? Chem. Phys. Lett. 2013, 570, 1 10.1016/j.cplett.2013.03.035
21. Pham, P.; Calabrese, P.; Park, S. J.; Goodman, M. F. 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. 2011, 286, 24931-24942 10.1074/jbc.M111.241208
22. Chelico, L.; Pham, P.; Calabrese, P.; Goodman, M. F. APOBEC3G DNA Deaminase Acts Processively 3′ - > 5′ on Single-Stranded DNA Nat. Struct. Mol. Biol. 2006, 13, 392-399 10.1038/nsmb1086
23. Chelico, L.; Sacho, E. J.; Erie, D. A.; Goodman, M. F. A Model for Oligomeric Regulation of APOBEC3G Cytosine Deaminase-Dependent Restriction of HIV J. Biol. Chem. 2008, 283, 13780-13791 10.1074/jbc.M801004200
24. Senavirathne, G.; Jaszczur, M.; Auerbach, P. A.; Upton, T. G.; Chelico, L.; Goodman, M. F.; Rueda, D. Single-Stranded DNA Scanning and Deamination by APOBEC3G Cytidine Deaminase at Single Molecule Resolution J. Biol. Chem. 2012, 287, 15826-15835 10.1074/jbc.M112.342790
25. Nowarski, R.; Britan-Rosich, E.; Shiloach, T.; Kotler, M. Hypermutation by Intersegmental Transfer of APOBEC3G Cytidine Deaminase Nat. Struct. Mol. Biol. 2008, 15, 1059-1066 10.1038/nsmb.1495
26. Ara, A.; Love, R. P.; Chelico, L. Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms PLoS Pathog. 2014, 10, e1004024 10.1371/journal.ppat.1004024
27. Pham, P.; Landolph, A.; Mendez, C.; Li, N.; Goodman, M. F. A Biochemical Analysis Linking APOBEC3A to Disparate HIV-1 Restriction and Skin Cancer J. Biol. Chem. 2013, 288, 29294-29304 10.1074/jbc.M113.504175
28. Logue, E. C.; Bloch, N.; Dhuey, E.; Zhang, R.; Cao, P.; Herate, C.; Chauveau, L.; Hubbard, S. R.; Landau, N. R. A DNA Sequence Recognition Loop on APOBEC3A Controls Substrate Specificity PLoS One 2014, 9, e97062 10.1371/journal.pone.0097062
29. Love, R. P.; Xu, H.; Chelico, L. Biochemical Analysis of Hypermutation by the Deoxycytidine Deaminase APOBEC3A J. Biol. Chem. 2012, 287, 30812-30822 10.1074/jbc.M112.393181
30. Prochnow, C.; Bransteitter, R.; Klein, M. G.; Goodman, M. F.; Chen, X. S. The APOBEC-2 Crystal Structure and Functional Implications for the Deaminase AID Nature 2007, 445, 447-451 10.1038/nature05492
31. Byeon, I. J.; Ahn, J.; Mitra, M.; Byeon, C. H.; Hercik, K.; Hritz, J.; Charlton, L. M.; Levin, J. G.; Gronenborn, A. M. Nmr Structure of Human Restriction Factor APOBEC3A Reveals Substrate Binding and Enzyme Specificity Nat. Commun. 2013, 4, 1890 10.1038/ncomms2883
32. Bohn, M. F.; Shandilya, S. M.; Silvas, T. V.; Nalivaika, E. A.; Kouno, T.; Kelch, B. A.; Ryder, S. P.; Kurt-Yilmaz, N.; Somasundaran, M.; Schiffer, C. A. The Ssdna Mutator APOBEC3A Is Regulated by Cooperative Dimerization Structure 2015, 23, 903-911 10.1016/j.str.2015.03.016
33. Kitamura, S.; Ode, H.; Nakashima, M.; Imahashi, M.; Naganawa, Y.; Kurosawa, T.; Yokomaku, Y.; Yamane, T.; Watanabe, N.; Suzuki, A. et al. The APOBEC3C Crystal Structure and the Interface for HIV-1 Vif Binding Nat. Struct. Mol. Biol. 2012, 19, 1005-1010 10.1038/nsmb.2378
34. Shi, K.; Carpenter, M. A.; Kurahashi, K.; Harris, R. S.; Aihara, H. Crystal Structure of the DNA Deaminase APOBEC3B Catalytic Domain J. Biol. Chem. 2015, 290, 28120-28130 10.1074/jbc.M115.679951
35. Bohn, M. F.; Shandilya, S. M.; Albin, J. S.; Kouno, T.; Anderson, B. D.; McDougle, R. M.; Carpenter, M. A.; Rathore, A.; Evans, L.; Davis, A. N. et al. Crystal Structure of the DNA Cytosine Deaminase APOBEC3F: The Catalytically Active and HIV-1 Vif-Binding Domain Structure 2013, 21, 1042-1050 10.1016/j.str.2013.04.010
36. Siu, K. K.; Sultana, A.; Azimi, F. C.; Lee, J. E. Structural Determinants of HIV-1 Vif Susceptibility and DNA Binding in APOBEC3F Nat. Commun. 2013, 4, 2593 10.1038/ncomms3593
37. Chen, K. M.; Harjes, E.; Gross, P. J.; Fahmy, A.; Lu, Y.; Shindo, K.; Harris, R. S.; Matsuo, H. Structure of the DNA Deaminase Domain of the HIV-1 Restriction Factor APOBEC3G Nature 2008, 452, 116-119 10.1038/nature06638
38. Furukawa, A.; Nagata, T.; Matsugami, A.; Habu, Y.; Sugiyama, R.; Hayashi, F.; Kobayashi, N.; Yokoyama, S.; Takaku, H.; Katahira, M. Structure, Interaction and Real-Time Monitoring of the Enzymatic Reaction of Wild-Type APOBEC3G EMBO J. 2009, 28, 440-451 10.1038/emboj.2008.290
39. Harjes, E.; Gross, P. J.; Chen, K. M.; Lu, Y.; Shindo, K.; Nowarski, R.; Gross, J. D.; Kotler, M.; Harris, R. S.; Matsuo, H. An Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model J. Mol. Biol. 2009, 389, 819-832 10.1016/j.jmb.2009.04.031
40. Holden, L. G.; Prochnow, C.; Chang, Y. P.; Bransteitter, R.; Chelico, L.; Sen, U.; Stevens, R. C.; Goodman, M. F.; Chen, X. S. Crystal Structure of the Anti-Viral APOBEC3G Catalytic Domain and Functional Implications Nature 2008, 456, 121-124 10.1038/nature07357
41. Kouno, T.; Luengas, E. M.; Shigematsu, M.; Shandilya, S. M.; Zhang, J.; Chen, L.; Hara, M.; Schiffer, C. A.; Harris, R. S.; Matsuo, H. Structure of the Vif-Binding Domain of the Antiviral Enzyme APOBEC3G Nat. Struct. Mol. Biol. 2015, 22, 485-491 10.1038/nsmb.3033
42. King, J. J.; Manuel, C. A.; Barrett, C. V.; Raber, S.; Lucas, H.; Sutter, P.; Larijani, M. Catalytic Pocket Inaccessibility of Activation-Induced Cytidine Deaminase Is a Safeguard against Excessive Mutagenic Activity Structure 2015, 23, 615-627 10.1016/j.str.2015.01.016
43. Pham, P.; Afif, S. A.; Shimoda, M.; Maeda, K.; Sakaguchi, N.; Pedersen, L. C.; Goodman, M. F. Structural Analysis of the Activation-Induced Deoxycytidine Deaminase Required in Immunoglobulin Diversification DNA Repair 2016, 43, 48-56 10.1016/j.dnarep.2016.05.029
44. Robert, X.; Gouet, P. Deciphering Key Features in Protein Structures with the New Endscript Server Nucleic Acids Res. 2014, 42, W320-324 10.1093/nar/gku316
45. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSFChimera - a Visualization System for Exploratory Research and Analysis J. Comput. Chem. 2004, 25, 1605-1612 10.1002/jcc.20084
46. Carpenter, M. A.; Rajagurubandara, E.; Wijesinghe, P.; Bhagwat, A. S. Determinants of Sequence-Specificity within Human AID and APOBEC3G DNA Repair 2010, 9, 579-587 10.1016/j.dnarep.2010.02.010
47. Kohli, R. M.; Abrams, S. R.; Gajula, K. S.; Maul, R. W.; Gearhart, P. J.; Stivers, J. T. A Portable Hot Spot Recognition Loop Transfers Sequence Preferences from APOBEC Family Members to Activation-Induced Cytidine Deaminase J. Biol. Chem. 2009, 284, 22898-22904 10.1074/jbc.M109.025536
48. Wang, M.; Rada, C.; Neuberger, M. S. Altering the Spectrum of Immunoglobulin V Gene Somatic Hypermutation by Modifying the Active Site of AID J. Exp. Med. 2010, 207, 141-153 10.1084/jem.20092238
49. Bulliard, Y.; Narvaiza, I.; Bertero, A.; Peddi, S.; Rohrig, U. F.; Ortiz, M.; Zoete, V.; Castro-Diaz, N.; Turelli, P.; Telenti, A. et al. Structure-Function Analyses Point to a Polynucleotide-Accommodating Groove Essential for APOBEC3A Restriction Activities J. Virol. 2011, 85, 1765-1776 10.1128/JVI.01651-10
50. Gajula, K. S.; Huwe, P. J.; Mo, C. Y.; Crawford, D. J.; Stivers, J. T.; Radhakrishnan, R.; Kohli, R. M. High-Throughput Mutagenesis Reveals Functional Determinants for DNA Targeting by Activation-Induced Deaminase Nucleic Acids Res. 2014, 42, 9964-9975 10.1093/nar/gku689
51. Rathore, A.; Carpenter, M. A.; Demir, O.; Ikeda, T.; Li, M.; Shaban, N. M.; Law, E. K.; Anokhin, D.; Brown, W. L.; Amaro, R. E. et al. The Local Dinucleotide Preference of APOBEC3G Can Be Altered from 5′-CC to 5′-TC by a Single Amino Acid Substitution J. Mol. Biol. 2013, 425, 4442-4454 10.1016/j.jmb.2013.07.040
52. Chen, Q.; Xiao, X.; Wolfe, A.; Chen, X. S. The in Vitro Biochemical Characterization of an HIV-1 Restriction Factor APOBEC3F: Importance of Loop 7 on Both Cd1 and Cd2 for DNA Binding and Deamination J. Mol. Biol. 2016, 428, 2661-2670 10.1016/j.jmb.2016.03.031
53. 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 10.1074/jbc.M408135200
54. Brar, S. S.; Sacho, E. J.; Tessmer, I.; Croteau, D. L.; Erie, D. A.; Diaz, M. Activation-Induced Deaminase, AID, Is Catalytically Active as a Monomer on Single-Stranded DNA DNA Repair 2008, 7, 77-87 10.1016/j.dnarep.2007.08.002
55. Shlyakhtenko, L. S.; Lushnikov, A. J.; Li, M.; Harris, R. S.; Lyubchenko, Y. L. Interaction of APOBEC3A with DNA Assessed by Atomic Force Microscopy PLoS One 2014, 9, e99354 10.1371/journal.pone.0099354
56. Shlyakhtenko, L. S.; Lushnikov, A. Y.; Li, M.; Lackey, L.; Harris, R. S.; Lyubchenko, Y. L. Atomic Force Microscopy Studies Provide Direct Evidence for Dimerization of the HIV Restriction Factor APOBEC3G J. Biol. Chem. 2011, 286, 3387-3395 10.1074/jbc.M110.195685
57. Chiu, Y. L. Biochemical Fractionation and Purification of High-Molecular-Mass APOBEC3G Complexes Methods Mol. Biol. 2011, 718, 185-206 10.1007/978-1-61779-018-8-12
58. Goila-Gaur, R.; Khan, M. A.; Miyagi, E.; Kao, S.; Opi, S.; Takeuchi, H.; Strebel, K. HIV-1 Vif Promotes the Formation of High Molecular Mass APOBEC3G Complexes Virology 2008, 372, 136-146 10.1016/j.virol.2007.10.017
59. Huthoff, H.; Autore, F.; Gallois-Montbrun, S.; Fraternali, F.; Malim, M. H. RNA-Dependent Oligomerization of APOBEC3G Is Required for Restriction of HIV-1 PLoS Pathog. 2009, 5, e1000330 10.1371/journal.ppat.1000330
60. Li, J.; Chen, Y.; Li, M.; Carpenter, M. A.; McDougle, R. M.; Luengas, E. M.; Macdonald, P. J.; Harris, R. S.; Mueller, J. D. APOBEC3Multimerization Correlates with HIV-1 Packaging and Restriction Activity in Living Cells J. Mol. Biol. 2014, 426, 1296-1307 10.1016/j.jmb.2013.12.014
61. Nair, S.; Sanchez-Martinez, S.; Ji, X.; Rein, A. Biochemical and Biological Studies of Mouse APOBEC3 J. Virol. 2014, 88, 3850-3860 10.1128/JVI.03456-13
62. Wedekind, J. E.; Gillilan, R.; Janda, A.; Krucinska, J.; Salter, J. D.; Bennett, R. P.; Raina, J.; Smith, H. C. Nanostructures of APOBEC3G Support a Hierarchical Assembly Model of High Molecular Mass Ribonucleoprotein Particles from Dimeric Subunits J. Biol. Chem. 2006, 281, 38122-38126 10.1074/jbc.C600253200
63. Siriwardena, S. U.; Guruge, T. A.; Bhagwat, A. S. Characterization of the Catalytic Domain of Human APOBEC3B and the Critical Structural Role for a Conserved Methionine J. Mol. Biol. 2015, 427, 3042-3055 10.1016/j.jmb.2015.08.006
64. Shirakawa, K.; Takaori-Kondo, A.; Yokoyama, M.; Izumi, T.; Matsui, M.; Io, K.; Sato, T.; Sato, H.; Uchiyama, T. Phosphorylation of APOBEC3G by Protein Kinase a Regulates Its Interaction with HIV-1 Vif Nat. Struct. Mol. Biol. 2008, 15, 1184-1191 10.1038/nsmb.1497
65. Chelico, L.; Prochnow, C.; Erie, D. A.; Chen, X. S.; Goodman, M. F. Structural Model for Deoxycytidine Deamination Mechanisms of the HIV-1 Inactivation Enzyme APOBEC3G J. Biol. Chem. 2010, 285, 16195-16205 10.1074/jbc.M110.107987
66. Belanger, K.; Savoie, M.; Rosales Gerpe, M. C.; Couture, J. F.; Langlois, M. A. Binding of RNA by APOBEC3G Controls Deamination-Independent Restriction of Retroviruses Nucleic Acids Res. 2013, 41, 7438-7452 10.1093/nar/gkt527
67. Friew, Y. N.; Boyko, V.; Hu, W. S.; Pathak, V. K. Intracellular Interactions between APOBEC3G, RNA, and HIV-1 Gag: APOBEC3G Multimerization Is Dependent on Its Association with RNA Retrovirology 2009, 6, 56 10.1186/1742-4690-6-56
68. Lavens, D.; Peelman, F.; Van der Heyden, J.; Uyttendaele, I.; Catteeuw, D.; Verhee, A.; Van Schoubroeck, B.; Kurth, J.; Hallenberger, S.; Clayton, R. et al. Definition of the Interacting Interfaces of APOBEC3G and HIV-1 Vif Using Mappit Mutagenesis Analysis Nucleic Acids Res. 2010, 38, 1902-1912 10.1093/nar/gkp1154
69. Russell, R. A.; Smith, J.; Barr, R.; Bhattacharyya, D.; Pathak, V. K. Distinct Domains within APOBEC3G and APOBEC3F Interact with Separate Regions of Human Immunodeficiency Virus Type 1 Vif J. Virol. 2009, 83, 1992-2003 10.1128/JVI.01621-08
70. Burnett, A.; Spearman, P. 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. 2007, 81, 5000-5013 10.1128/JVI.02237-06
71. Hodges, P.; Scott, J. Apolipoprotein B mRNA Editing: A New Tier for the Control of Gene Expression Trends Biochem. Sci. 1992, 17, 77-81 10.1016/0968-0004(92)90506-5
72. 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 10.1016/S0092-8674(00)00078-7
73. Stavrou, S.; Ross, S. R. APOBEC3 Proteins in Viral Immunity J. Immunol. 2015, 195, 4565-4570 10.4049/jimmunol.1501504
74. Willems, L.; Gillet, N. A. APOBEC3 Interference During Replication of Viral Genomes Viruses 2015, 7, 2999-3018 10.3390/v7062757
75. Kato, L.; Begum, N. A.; Burroughs, A. M.; Doi, T.; Kawai, J.; Daub, C. O.; Kawaguchi, T.; Matsuda, F.; Hayashizaki, Y.; Honjo, T. Nonimmunoglobulin Target Loci of Activation-Induced Cytidine Deaminase (AID) Share Unique Features with Immunoglobulin Genes Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 2479-2484 10.1073/pnas.1120791109
76. Burnet, F. M. A Modification of Jerne's Theory of Antibody Production Using the Concept of Clonal Selection Aust J. Sci. 1957, 20, 67-69
77. Burnet, F. M. The Clonal Selection Theory of Acquired Immunity; Cambridge University Press: Cambridge, England, 1959.
78. Talmage, D. W. Allergy and Immunology Annu. Rev. Med. 1957, 8, 239-256 10.1146/annurev.me.08.020157.001323
79. Rajewsky, K. Clonal Selection and Learning in the Antibody System Nature 1996, 381, 751-758 10.1038/381751a0
80. Victora, G. D.; Mesin, L. Clonal and Cellular Dynamics in Germinal Centers Curr. Opin. Immunol. 2014, 28, 90-96 10.1016/j.coi.2014.02.010
81. Victora, G. D.; Nussenzweig, M. C. Germinal Centers Annu. Rev. Immunol. 2012, 30, 429-457 10.1146/annurev-immunol-020711-075032
82. Maizels, N.; Scharff, M. D. In Molecular Biology of B Cells; Honjo, T.; Alt, F. W.; Neuberger, M. S., Eds.; Elsevier Academic Press: London, 2004.
83. Arakawa, H.; Hauschild, J.; Buerstedde, J. M. Requirement of the Activation-Induced Deaminase (AID) Gene for Immunoglobulin Gene Conversion Science 2002, 295, 1301-1306 10.1126/science.1067308
84. Harris, R. S.; Sale, J. E.; Petersen-Mahrt, S. K.; Neuberger, M. S. AID Is Essential for Immunoglobulin V Gene Conversion in a Cultured B Cell Line Curr. Biol. 2002, 12, 435-438 10.1016/S0960-9822(02)00717-0
85. Di Noia, J. M.; Neuberger, M. S. Molecular Mechanisms of Antibody Somatic Hypermutation Annu. Rev. Biochem. 2007, 76, 1-22 10.1146/annurev.biochem.76.061705.090740
86. Rogozin, I. B.; Kolchanov, N. A. Somatic Hypermutagenesis in Immunoglobulin Genes. Ii. Influence of Neighbouring Base Sequences on Mutagenesis Biochim. Biophys. Acta, Gene Struct. Expression 1992, 1171, 11-18 10.1016/0167-4781(92)90134-L
87. Rogozin, I. B.; Basu, M. K.; Jordan, I. K.; Pavlov, Y. I.; Koonin, E. V. APOBEC4, a New Member of the AID/APOBEC Family of Polynucleotide (Deoxy)Cytidine Deaminases Predicted by Computational Analysis Cell Cycle 2005, 4, 1281-1285 10.4161/cc.4.9.1994
88. 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 10.1038/nature00862
89. Masutani, C.; Kusumoto, R.; Iwai, S.; Hanaoka, F. Mechanisms of Accurate Translesion Synthesis by Human DNA Polymerase Eta EMBO J. 2000, 19, 3100-3109 10.1093/emboj/19.12.3100
90. Lawrence, C. W.; Hinkle, D. C. DNA Polymerase Zeta and the Control of DNA Damage Induced Mutagenesis in Eukaryotes Cancer Surv. 1996, 28, 21-31
91. Prakash, S.; Johnson, R. E.; Prakash, L. Eukaryotic Translesion Synthesis DNA Polymerases: Specificity of Structure and Function Annu. Rev. Biochem. 2005, 74, 317-353 10.1146/annurev.biochem.74.082803.133250
92. Rada, C.; Di Noia, J. M.; Neuberger, M. S. Mismatch Recognition and Uracil Excision Provide Complementary Paths to Both Ig Switching and the a/T-Focused Phase of Somatic Mutation Mol. Cell 2004, 16, 163-171 10.1016/j.molcel.2004.10.011
93. Shen, H. M.; Tanaka, A.; Bozek, G.; Nicolae, D.; Storb, U. Somatic Hypermutation and Class Switch Recombination in Msh6(-/-)Ung(-/-) Double-Knockout Mice J. Immunol. 2006, 177, 5386-5392 10.4049/jimmunol.177.8.5386
94. Casali, P.; Pal, Z.; Xu, Z.; Zan, H. DNA Repair in Antibody Somatic Hypermutation Trends Immunol. 2006, 27, 313-321 10.1016/j.it.2006.05.001
95. Neuberger, M. S.; Rada, C. Somatic Hypermutation: Activation-Induced Deaminase for C/G Followed by Polymerase eta for A/T J. Exp. Med. 2007, 204, 7-10 10.1084/jem.20062409
96. Zanotti, K. J.; Gearhart, P. J. Antibody Diversification Caused by Disrupted Mismatch Repair and Promiscuous DNA Polymerases DNA Repair 2016, 38, 110 10.1016/j.dnarep.2015.11.011
97. Peters, A.; Storb, U. Somatic Hypermutation of Immunoglobulin Genes Is Linked to Transcription Initiation Immunity 1996, 4, 57-65 10.1016/S1074-7613(00)80298-8
98. Storb, U. The Molecular Basis of Somatic Hypermutation of Immunoglobulin Genes Curr. Opin. Immunol. 1996, 8, 206-214 10.1016/S0952-7915(96)80059-8
99. Jinks-Robertson, S.; Bhagwat, A. S. Transcription-Associated Mutagenesis Annu. Rev. Genet. 2014, 48, 341-359 10.1146/annurev-genet-120213-092015
100. Mak, C. H.; Pham, P.; Afif, S. A.; Goodman, M. F. A Mathematical Model for Scanning and Catalysis on Single-Stranded DNA, Illustrated with Activation-Induced Deoxycytidine Deaminase J. Biol. Chem. 2013, 288, 29786-29795 10.1074/jbc.M113.506550
101. Mak, C. H.; Pham, P.; Afif, S. A.; Goodman, M. F. Random-Walk Enzymes Physical review. E, Statistical, nonlinear, and soft matter physics 2015, 92, 032717-032717 10.1103/PhysRevE.92.032717
102. Bhagwat, A. S. DNA-Cytosine Deaminases: From Antibody Maturation to Antiviral Defense DNA Repair 2004, 3, 85-89 10.1016/j.dnarep.2003.09.008
103. Canugovi, C.; Samaranayake, M.; Bhagwat, A. S. Transcriptional Pausing and Stalling Causes Multiple Clustered Mutations by Human Activation-Induced Deaminase FASEB J. 2009, 23, 34-44 10.1096/fj.08-115352
104. Gnatt, A. L.; Cramer, P.; Fu, J.; Bushnell, D. A.; Kornberg, R. D. Structural Basis of Transcription: An RNA Polymerase Ii Elongation Complex at 3.3 a Resolution Science 2001, 292, 1876-1882 10.1126/science.1059495
105. Basu, U.; Meng, F. L.; Keim, C.; Grinstein, V.; Pefanis, E.; Eccleston, J.; Zhang, T.; Myers, D.; Wasserman, C. R.; Wesemann, D. R. et al. The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of Transcribed Duplex DNA Substrates Cell 2011, 144, 353-363 10.1016/j.cell.2011.01.001
106. Pefanis, E.; Basu, U. RNA Exosome Regulates AID DNA Mutator Activity in the B Cell Genome Adv. Immunol. 2015, 127, 257-308 10.1016/bs.ai.2015.04.002
107. Pefanis, E.; Wang, J.; Rothschild, G.; Lim, J.; Chao, J.; Rabadan, R.; Economides, A. N.; Basu, U. Noncoding RNA Transcription Targets AID to Divergently Transcribed Loci in B Cells Nature 2014, 514, 389-393 10.1038/nature13580
108. Wright, B. E.; Schmidt, K. H.; Davis, N.; Hunt, A. T.; Minnick, M. F., Ii. Correlations between Secondary Structure Stability and Mutation Frequency During Somatic Hypermutation Mol. Immunol. 2008, 45, 3600-3608 10.1016/j.molimm.2008.05.012
109. Wright, B. E.; Schmidt, K. H.; Minnick, M. F.; Davis, N. I. Vh Gene Transcription Creates Stabilized Secondary Structures for Coordinated Mutagenesis During Somatic Hypermutation Mol. Immunol. 2008, 45, 3589-3599 10.1016/j.molimm.2008.02.030
110. Shen, H. M.; Storb, U. Activation-Induced Cytidine Deaminase (AID) Can Target Both DNA Strands When the DNA Is Supercoiled Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 12997-13002 10.1073/pnas.0404974101
111. Casellas, R.; Basu, U.; Yewdell, W. T.; Chaudhuri, J.; Robbiani, D. F.; Di Noia, J. M. Mutations, Kataegis and Translocations in B Cells: Understanding AID Promiscuous Activity Nat. Rev. Immunol. 2016, 16, 164-176 10.1038/nri.2016.2
112. Senavirathne, G.; Bertram, J. G.; Jaszczur, M.; Chaurasiya, K. R.; Pham, P.; Mak, C. H.; Goodman, M. F.; Rueda, D. Activation-Induced Deoxycytidine Deaminase (AID) Co-Transcriptional Scanning at Single-Molecule Resolution Nat. Commun. 2015, 6, 10209 10.1038/ncomms10209
113. 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 10.1016/S0960-9822(02)01215-0
114. Phung, Q. H.; Winter, D. B.; Cranston, A.; Tarone, R. E.; Bohr, V. A.; Fishel, R.; Gearhart, P. J. Increased Hypermutation at G and C Nucleotides in Immunoglobulin Variable Genes from Mice Deficient in the Msh2Mismatch Repair Protein J. Exp. Med. 1998, 187, 1745-1751 10.1084/jem.187.11.1745
115. Maul, R. W.; Saribasak, H.; Martomo, S. A.; McClure, R. L.; Yang, W.; Vaisman, A.; Gramlich, H. S.; Schatz, D. G.; Woodgate, R.; Wilson, D. M., 3rd et al. Uracil Residues Dependent on the Deaminase AID in Immunoglobulin Gene Variable and Switch Regions Nat. Immunol. 2011, 12, 70-76 10.1038/ni.1970
116. Roche, B.; Claes, A.; Rougeon, F. Deoxyuridine Triphosphate Incorporation During Somatic Hypermutation of Mouse Vkox Genes after Immunization with Phenyloxazolone J. Immunol. 2010, 185, 4777-4782 10.4049/jimmunol.1001459
117. Shalhout, S.; Haddad, D.; Sosin, A.; Holland, T. C.; Al-Katib, A.; Martin, A.; Bhagwat, A. S. Genomic Uracil Homeostasis During Normal B Cell Maturation and Loss of This Balance During B Cell Cancer Development Mol. Cell. Biol. 2014, 34, 4019-4032 10.1128/MCB.00589-14
118. Mashiyama, S. T.; Hansen, C. M.; Roitman, E.; Sarmiento, S.; Leklem, J. E.; Shultz, T. D.; Ames, B. N. An Assay for Uracil in Human DNA at Baseline: Effect of Marginal Vitamin B6 Deficiency Anal. Biochem. 2008, 372, 21-31 10.1016/j.ab.2007.08.034
119. Stavnezer, J.; Guikema, J. E.; Schrader, C. E. Mechanism and Regulation of Class Switch Recombination Annu. Rev. Immunol. 2008, 26, 261-292 10.1146/annurev.immunol.26.021607.090248
120. Stavnezer, J.; Schrader, C. E. Igh Chain Class Switch Recombination: Mechanism and Regulation J. Immunol. 2014, 193, 5370-5378 10.4049/jimmunol.1401849
121. 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 10.1084/jem.20050872
122. Ehrenstein, M. R.; Neuberger, M. S. Deficiency in Msh2 Affects the Efficiency and Local Sequence Specificity of Immunoglobulin Class-Switch Recombination: Parallels with Somatic Hypermutation EMBO J. 1999, 18, 3484-3490 10.1093/emboj/18.12.3484
123. Schrader, C. E.; Edelmann, W.; Kucherlapati, R.; Stavnezer, J. Reduced Isotype Switching in Splenic B Cells from Mice Deficient in Mismatch Repair Enzymes J. Exp. Med. 1999, 190, 323-330 10.1084/jem.190.3.323
124. Masani, S.; Han, L.; Yu, K. Apurinic/Apyrimidinic Endonuclease 1 Is the Essential Nuclease During Immunoglobulin Class Switch Recombination Mol. Cell. Biol. 2013, 33, 1468-1473 10.1128/MCB.00026-13
125. Lindahl, T. Instability and Decay of the Primary Structure of DNA Nature 1993, 362, 709-715 10.1038/362709a0
126. 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 10.4049/jimmunol.179.9.6064
127. Sharbeen, G.; Yee, C. W.; Smith, A. L.; Jolly, C. J. Ectopic Restriction of DNA Repair Reveals That Ung2 Excises AID-Induced Uracils Predominantly or Exclusively During G1 Phase J. Exp. Med. 2012, 209, 965-974 10.1084/jem.20112379
128. Pena-Diaz, J.; Bregenhorn, S.; Ghodgaonkar, M.; Follonier, C.; Artola-Boran, M.; Castor, D.; Lopes, M.; Sartori, A. A.; Jiricny, J. Noncanonical Mismatch Repair as a Source of Genomic Instability in Human Cells Mol. Cell 2012, 47, 669-680 10.1016/j.molcel.2012.07.006
129. Bregenhorn, S.; Kallenberger, L.; Artola-Boran, M.; Pena-Diaz, J.; Jiricny, J. Non-Canonical Uracil Processing in DNA Gives Rise to Double-Strand Breaks and Deletions: Relevance to Class Switch Recombination Nucleic Acids Res. 2016, 44, 2691 10.1093/nar/gkv1535
130. Hasham, M. G.; Snow, K. J.; Donghia, N. M.; Branca, J. A.; Lessard, M. D.; Stavnezer, J.; Shopland, L. S.; Mills, K. D. Activation-Induced Cytidine Deaminase-Initiated Off-Target DNA Breaks Are Detected and Resolved During S Phase J. Immunol. 2012, 189, 2374-2382 10.4049/jimmunol.1200414
131. Dunnick, W.; Hertz, G. Z.; Scappino, L.; Gritzmacher, C. DNA Sequences at Immunoglobulin Switch Region Recombination Sites Nucleic Acids Res. 1993, 21, 365-372 10.1093/nar/21.3.365
132. Nagaoka, H.; Muramatsu, M.; Yamamura, N.; Kinoshita, K.; Honjo, T. Activation-Induced Deaminase (AID)-Directed Hypermutation in the Immunoglobulin Smu Region: Implication of AID Involvement in a Common Step of Class Switch Recombination and Somatic Hypermutation J. Exp. Med. 2002, 195, 529-534 10.1084/jem.20012144
133. 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 10.1084/jem.20061067
134. Morgan, H. D.; Dean, W.; Coker, H. A.; Reik, W.; Petersen-Mahrt, S. K. Activation-Induced Cytidine Deaminase Deaminates 5-Methylcytosine in DNA and Is Expressed in Pluripotent Tissues: Implications for Epigenetic Reprogramming J. Biol. Chem. 2004, 279, 52353-52360 10.1074/jbc.M407695200
135. Morgan, H. D.; Santos, F.; Green, K.; Dean, W.; Reik, W. Epigenetic Reprogramming in Mammals Hum. Mol. Genet. 2005, 14 (14 Spec No 1) R47-58 10.1093/hmg/ddi114
136. Reik, W. Stability and Flexibility of Epigenetic Gene Regulation in Mammalian Development Nature 2007, 447, 425-432 10.1038/nature05918
137. 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 10.1074/jbc.274.26.18470
138. Larijani, M.; Frieder, D.; Sonbuchner, T. M.; Bransteitter, R.; Goodman, M. F.; Bouhassira, E. E.; Scharff, M. D.; Martin, A. Methylation Protects Cytidines from AID-Mediated Deamination Mol. Immunol. 2005, 42, 599-604 10.1016/j.molimm.2004.09.007
139. Nabel, C. S.; Jia, H.; Ye, Y.; Shen, L.; Goldschmidt, H. L.; Stivers, J. T.; Zhang, Y.; Kohli, R. M. AID/APOBEC Deaminases Disfavor Modified Cytosines Implicated in DNA Demethylation Nat. Chem. Biol. 2012, 8, 751-758 10.1038/nchembio.1042
140. Rangam, G.; Schmitz, K. M.; Cobb, A. J.; Petersen-Mahrt, S. K. AID Enzymatic Activity Is Inversely Proportional to the Size of Cytosine C5 Orbital Cloud PLoS One 2012, 7, e43279 10.1371/journal.pone.0043279
141. Ito, S.; Shen, L.; Dai, Q.; Wu, S. C.; Collins, L. B.; Swenberg, J. A.; He, C.; Zhang, Y. Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine Science 2011, 333, 1300-1303 10.1126/science.1210597
142. Tahiliani, M.; Koh, K. P.; Shen, Y.; Pastor, W. A.; Bandukwala, H.; Brudno, Y.; Agarwal, S.; Iyer, L. M.; Liu, D. R.; Aravind, L. et al. Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by Mll Partner Tet1 Science 2009, 324, 930-935 10.1126/science.1170116
143. Gkountela, S.; Clark, A. T. A Big Surprise in the Little Zygote: The Curious Business of Losing Methylated Cytosines Cell Stem Cell 2014, 15, 393-394 10.1016/j.stem.2014.09.005
144. Nabel, C. S.; Manning, S. A.; Kohli, R. M. The Curious Chemical Biology of Cytosine: Deamination, Methylation, and Oxidation as Modulators of Genomic Potential ACS Chem. Biol. 2012, 7, 20-30 10.1021/cb2002895
145. Fritz, E. L.; Rosenberg, B. R.; Lay, K.; Mihailovic, A.; Tuschl, T.; Papavasiliou, F. N. A Comprehensive Analysis of the Effects of the Deaminase AID on the Transcriptome and Methylome of Activated B Cells Nat. Immunol. 2013, 14, 749-755 10.1038/ni.2616
146. Bhutani, N.; Decker, M. N.; Brady, J. J.; Bussat, R. T.; Burns, D. M.; Corbel, S. Y.; Blau, H. M. A Critical Role for AID in the Initiation of Reprogramming to Induced Pluripotent Stem Cells FASEB J. 2013, 27, 1107-1113 10.1096/fj.12-222125
147. Dominguez, P. M.; Teater, M.; Chambwe, N.; Kormaksson, M.; Redmond, D.; Ishii, J.; Vuong, B.; Chaudhuri, J.; Melnick, A.; Vasanthakumar, A. et al. DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID Cell Rep. 2015, 12, 2086-2098 10.1016/j.celrep.2015.08.036
148. Kumar, R.; DiMenna, L.; Schrode, N.; Liu, T. C.; Franck, P.; Munoz-Descalzo, S.; Hadjantonakis, A. K.; Zarrin, A. A.; Chaudhuri, J.; Elemento, O. et al. AID Stabilizes Stem-Cell Phenotype by Removing Epigenetic Memory of Pluripotency Genes Nature 2013, 500, 89-92 10.1038/nature12299
149. Munoz, D. P.; Lee, E. L.; Takayama, S.; Coppe, J. P.; Heo, S. J.; Boffelli, D.; Di Noia, J. M.; Martin, D. I. Activation-Induced Cytidine Deaminase (AID) Is Necessary for the Epithelial-Mesenchymal Transition in Mammary Epithelial Cells Proc. Natl. Acad. Sci. U. S. A. 2013, 110, E2977-2986 10.1073/pnas.1301021110
150. Ramiro, A. R.; Barreto, V. M. Activation-Induced Cytidine Deaminase and Active Cytidine Demethylation Trends Biochem. Sci. 2015, 40, 172-181 10.1016/j.tibs.2015.01.006
151. Nambu, Y.; Sugai, M.; Gonda, H.; Lee, C. G.; Katakai, T.; Agata, Y.; Yokota, Y.; Shimizu, A. Transcription-Coupled Events Associating with Immunoglobulin Switch Region Chromatin Science 2003, 302, 2137-2140 10.1126/science.1092481
152. 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 10.1038/ni.1964
153. 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 10.1038/nature06547
154. Chiarle, R.; Zhang, Y.; Frock, R. L.; Lewis, S. M.; Molinie, B.; Ho, Y. J.; Myers, D. R.; Choi, V. W.; Compagno, M.; Malkin, D. J. et al. Genome-Wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells Cell 2011, 147, 107-119 10.1016/j.cell.2011.07.049
155. Klein, I. A.; Resch, W.; Jankovic, M.; Oliveira, T.; Yamane, A.; Nakahashi, H.; Di Virgilio, M.; Bothmer, A.; Nussenzweig, A.; Robbiani, D. F. et al. Translocation-Capture Sequencing Reveals the Extent and Nature of Chromosomal Rearrangements in B Lymphocytes Cell 2011, 147, 95-106 10.1016/j.cell.2011.07.048
156. 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 10.1182/blood-2002-08-2424
157. Hardianti, M. S.; Tatsumi, E.; Syampurnawati, M.; Furuta, K.; Saigo, K.; Nakamachi, Y.; Kumagai, S.; Ohno, H.; Tanabe, S.; Uchida, M. et al. Activation-Induced Cytidine Deaminase Expression in Follicular Lymphoma: Association between AID Expression and Ongoing Mutation in Fl Leukemia 2004, 18, 826-831 10.1038/sj.leu.2403323
158. Lossos, I. S.; Levy, R.; Alizadeh, A. A. AID Is Expressed in Germinal Center B-Cell-Like and Activated B-Cell-Like Diffuse Large-Cell Lymphomas and Is Not Correlated with Intraclonal Heterogeneity Leukemia 2004, 18, 1775-1779 10.1038/sj.leu.2403488
159. 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 10.1182/blood-2004-04-1558
160. Smit, L. A.; Bende, R. J.; Aten, J.; Guikema, J. E.; Aarts, W. M.; van Noesel, C. J. Expression of Activation-Induced Cytidine Deaminase Is Confined to B-Cell Non-Hodgkin's Lymphomas of Germinal-Center Phenotype Cancer Res. 2003, 63, 3894-3898
161. Kuppers, R.; Dalla-Favera, R. Mechanisms of Chromosomal Translocations in B Cell Lymphomas Oncogene 2001, 20, 5580-5594 10.1038/sj.onc.1204640
162. Rabbitts, T. H. Chromosomal Translocations in Human Cancer Nature 1994, 372, 143-149 10.1038/372143a0
163. Gazumyan, A.; Bothmer, A.; Klein, I. A.; Nussenzweig, M. C.; McBride, K. M. Activation-Induced Cytidine Deaminase in Antibody Diversification and Chromosome Translocation Adv. Cancer Res. 2012, 113, 167-190 10.1016/B978-0-12-394280-7.00005-1
164. Gostissa, M.; Alt, F. W.; Chiarle, R. Mechanisms That Promote and Suppress Chromosomal Translocations in Lymphocytes Annu. Rev. Immunol. 2011, 29, 319-350 10.1146/annurev-immunol-031210-101329
165. Robbiani, D. F.; Nussenzweig, M. C. In Annual Review of Pathology: Mechanisms of Disease, Vol. 8; Abbas, A. K.; Galli, S. J.; Howley, P. M., Eds.; 2013; Vol. 8.
166. Potter, M. Neoplastic Development in Plasma Cells Immunol. Rev. 2003, 194, 177-195 10.1034/j.1600-065X.2003.00061.x
167. Potter, M.; Wiener, F. Plasmacytomagenesis in Mice: Model of Neoplastic Development Dependent Upon Chromosomal Translocations Carcinogenesis 1992, 13, 1681-1697 10.1093/carcin/13.10.1681
168. 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 10.1016/j.cell.2004.08.006
169. 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. et al. AID Is Required for the Chromosomal Breaks in C-Myc That Lead to C-Myc/Igh Translocations Cell 2008, 135, 1028-1038 10.1016/j.cell.2008.09.062
170. Pasqualucci, L.; Bhagat, G.; Jankovic, M.; Compagno, M.; Smith, P.; Muramatsu, M.; Honjo, T.; Morse, H. C., 3rd; Nussenzweig, M. C.; Dalla-Favera, R. AID Is Required for Germinal Center-Derived Lymphomagenesis Nat. Genet. 2008, 40, 108-112 10.1038/ng.2007.35
171. Komeno, Y.; Kitaura, J.; Watanabe-Okochi, N.; Kato, N.; Oki, T.; Nakahara, F.; Harada, Y.; Harada, H.; Shinkura, R.; Nagaoka, H. et al. AID-Induced T-Lymphoma or B-Leukemia/Lymphoma in a Mouse BMT Model Leukemia 2010, 24, 1018-1024 10.1038/leu.2010.40
172. 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 10.1084/jem.20030275
173. Okazaki, I. M.; Kotani, A.; Honjo, T. Role of AID in Tumorigenesis Adv. Immunol. 2007, 94, 245-273 10.1016/S0065-2776(06)94008-5
174. 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. U. S. A. 2005, 102, 4506-4511 10.1073/pnas.0500830102
175. Hatada, E. N.; Krappmann, D.; Scheidereit, C. NF-KappaB and the Innate Immune Response Curr. Opin. Immunol. 2000, 12, 52-58 10.1016/S0952-7915(99)00050-3
176. Mogensen, T. H.; Paludan, S. R. Molecular Pathways in Virus-Induced Cytokine Production Microbiol. Mol. Biol. Rev. 2001, 65, 131-150 10.1128/MMBR.65.1.131-150.2001
177. Jiang, C.; Foley, J.; Clayton, N.; Kissling, G.; Jokinen, M.; Herbert, R.; Diaz, M. Abrogation of Lupus Nephritis in Activation-Induced Deaminase-Deficient Mrl/Lpr Mice J. Immunol. 2007, 178, 7422-7431 10.4049/jimmunol.178.11.7422
178. 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 10.1038/sj.onc.1210344
179. Watashi, K.; Liang, G.; Iwamoto, M.; Marusawa, H.; Uchida, N.; Daito, T.; Kitamura, K.; Muramatsu, M.; Ohashi, H.; Kiyohara, T. et al. Interleukin-1 and Tumor Necrosis Factor-Alpha Trigger Restriction of Hepatitis B Virus Infection Via a Cytidine Deaminase Activation-Induced Cytidine Deaminase (AID) J. Biol. Chem. 2013, 288, 31715-31727 10.1074/jbc.M113.501122
180. 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 10.1053/j.gastro.2008.06.091
181. Dedeoglu, F.; Horwitz, B.; Chaudhuri, J.; Alt, F. W.; Geha, R. S. Induction of Activation-Induced Cytidine Deaminase Gene Expression by Il-4 and Cd40 Ligation Is Dependent on Stat6 and Nfkappab Int. Immunol. 2004, 16, 395-404 10.1093/intimm/dxh042
182. Revy, P.; Muto, T.; Levy, Y.; Geissmann, F.; Plebani, A.; Sanal, O.; Catalan, N.; Forveille, M.; Dufourcq-Labelouse, R.; Gennery, A. et al. Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-Igm Syndrome (Higm2) Cell 2000, 102, 565-575 10.1016/S0092-8674(00)00079-9
183. Quartier, P.; Bustamante, J.; Sanal, O.; Plebani, A.; Debre, M.; Deville, A.; Litzman, J.; Levy, J.; Fermand, J. P.; Lane, P. et al. Clinical, Immunologic and Genetic Analysis of 29 Patients with Autosomal Recessive Hyper-Igm Syndrome Due to Activation-Induced Cytidine Deaminase Deficiency Clin. Immunol. 2004, 110, 22-29 10.1016/j.clim.2003.10.007
184. Meyers, G.; Ng, Y. S.; Bannock, J. M.; Lavoie, A.; Walter, J. E.; Notarangelo, L. D.; Kilic, S. S.; Aksu, G.; Debre, M.; Rieux-Laucat, F. et al. Activation-Induced Cytidine Deaminase (AID) Is Required for B-Cell Tolerance in Humans Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 11554-11559 10.1073/pnas.1102600108
185. Wardemann, H.; Yurasov, S.; Schaefer, A.; Young, J. W.; Meffre, E.; Nussenzweig, M. C. Predominant Autoantibody Production by Early Human B Cell Precursors Science 2003, 301, 1374-1377 10.1126/science.1086907
186. Cantaert, T.; Schickel, J. N.; Bannock, J. M.; Ng, Y. S.; Massad, C.; Oe, T.; Wu, R.; Lavoie, A.; Walter, J. E.; Notarangelo, L. D. et al. Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance Immunity 2015, 43, 884-895 10.1016/j.immuni.2015.10.002
187. Kuraoka, M.; Holl, T. M.; Liao, D.; Womble, M.; Cain, D. W.; Reynolds, A. E.; Kelsoe, G. Activation-Induced Cytidine Deaminase Mediates Central Tolerance in B Cells Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 11560-11565 10.1073/pnas.1102571108
188. Rosenspire, A. J.; Chen, K. Anergic B Cells: Precarious on-Call Warriors at the Nexus of Autoimmunity and False-Flagged Pathogens Front. Immunol. 2015, 6, 580 10.3389/fimmu.2015.00580
189. Chen, L.; Guo, L.; Tian, J.; Zheng, B.; Han, S. Deficiency in Activation-Induced Cytidine Deaminase Promotes Systemic Autoimmunity in Lpr Mice on a C57bl/6 Background Clin. Exp. Immunol. 2010, 159, 169-175 10.1111/j.1365-2249.2009.04058.x
190. Hase, K.; Takahashi, D.; Ebisawa, M.; Kawano, S.; Itoh, K.; Ohno, H. Activation-Induced Cytidine Deaminase Deficiency Causes Organ-Specific Autoimmune Disease PLoS One 2008, 3, e3033 10.1371/journal.pone.0003033
191. Vinuesa, C. G.; Sanz, I.; Cook, M. C. Dysregulation of Germinal Centres in Autoimmune Disease Nat. Rev. Immunol. 2009, 9, 845-857 10.1038/nri2637
192. Xu, X.; Hsu, H. C.; Chen, J.; Grizzle, W. E.; Chatham, W. W.; Stockard, C. R.; Wu, Q.; Yang, P. A.; Holers, V. M.; Mountz, J. D. Increased Expression of Activation-Induced Cytidine Deaminase Is Associated with Anti-Ccp and Rheumatoid Factor in Rheumatoid Arthritis Scand. J. Immunol. 2009, 70, 309-316 10.1111/j.1365-3083.2009.02302.x
193. Hsu, H. C.; Wu, Y.; Yang, P.; Wu, Q.; Job, G.; Chen, J.; Wang, J.; Accavitti-Loper, M. A.; Grizzle, W. E.; Carter, R. H. et al. Overexpression of Activation-Induced Cytidine Deaminase in B Cells Is Associated with Production of Highly Pathogenic Autoantibodies J. Immunol. 2007, 178, 5357-5365 10.4049/jimmunol.178.8.5357
194. Guo, W.; Smith, D.; Aviszus, K.; Detanico, T.; Heiser, R. A.; Wysocki, L. J. Somatic Hypermutation as a Generator of Antinuclear Antibodies in a Murine Model of Systemic Autoimmunity J. Exp. Med. 2010, 207, 2225-2237 10.1084/jem.20092712
195. Jiang, C.; Zhao, M. L.; Diaz, M. Activation-Induced Deaminase Heterozygous Mrl/Lpr Mice Are Delayed in the Production of High-Affinity Pathogenic Antibodies and in the Development of Lupus Nephritis Immunology 2009, 126, 102-113 10.1111/j.1365-2567.2008.02882.x
196. Chan, O. T.; Hannum, L. G.; Haberman, A. M.; Madaio, M. P.; Shlomchik, M. J. A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-Independent Role for B Cells in Murine Lupus J. Exp. Med. 1999, 189, 1639-1648 10.1084/jem.189.10.1639
197. Qin, H.; Suzuki, K.; Nakata, M.; Chikuma, S.; Izumi, N.; Huong le, T.; Maruya, M.; Fagarasan, S.; Busslinger, M.; Honjo, T. et al. Activation-Induced Cytidine Deaminase Expression in Cd4+ T Cells Is Associated with a Unique Il-10-Producing Subset That Increases with Age PLoS One 2011, 6, e29141 10.1371/journal.pone.0029141
198. Bacchetta, R.; Notarangelo, L. D. Immunodeficiency with Autoimmunity: Beyond the Paradox Front. Immunol. 2013, 4, 77 10.3389/fimmu.2013.00077
199. Qian, X.; Balestra, M. E.; Yamanaka, S.; Boren, J.; Lee, I.; Innerarity, T. L. Low Expression of the Apolipoprotein B mRNA-Editing Transgene in Mice Reduces Ldl Levels but Does Not Cause Liver Dysplasia or Tumors Arterioscler., Thromb., Vasc. Biol. 1998, 18, 1013-1020 10.1161/01.ATV.18.6.1013
200. Greeve, J.; Altkemper, I.; Dieterich, J. H.; Greten, H.; Windler, E. Apolipoprotein B mRNA Editing in 12 Different Mammalian Species: Hepatic Expression Is Reflected in Low Concentrations of Apob-Containing Plasma Lipoproteins J. Lipid Res. 1993, 34, 1367-1383
201. Glickman, R. M.; Rogers, M.; Glickman, J. N. Apolipoprotein B Synthesis by Human Liver and Intestine in Vitro Proc. Natl. Acad. Sci. U. S. A. 1986, 83, 5296-5300 10.1073/pnas.83.14.5296
202. Kane, J. P.; Hardman, D. A.; Paulus, H. E. Heterogeneity of Apolipoprotein B: Isolation of a New Species from Human Chylomicrons Proc. Natl. Acad. Sci. U. S. A. 1980, 77, 2465-2469 10.1073/pnas.77.5.2465
203. Contois, J. H.; McConnell, J. P.; Sethi, A. A.; Csako, G.; Devaraj, S.; Hoefner, D. M.; Warnick, G. R. Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the Aacc Lipoproteins and Vascular Diseases Division Working Group on Best Practices Clin. Chem. 2009, 55, 407-419 10.1373/clinchem.2008.118356
204. 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 10.1126/science.3659919
205. Innerarity, T. L.; Boren, J.; Yamanaka, S.; Olofsson, S. O. Biosynthesis of Apolipoprotein B48-Containing Lipoproteins. Regulation by Novel Post-Transcriptional Mechanisms J. Biol. Chem. 1996, 271, 2353-2356 10.1074/jbc.271.5.2353
206. Lellek, H.; Kirsten, R.; Diehl, I.; Apostel, F.; Buck, F.; Greeve, J. Purification and Molecular Cloning of a Novel Essential Component of the Apolipoprotein B mRNA Editing Enzyme-Complex J. Biol. Chem. 2000, 275, 19848-19856 10.1074/jbc.M001786200
207. Mehta, A.; Kinter, M. T.; Sherman, N. E.; Driscoll, D. M. Molecular Cloning of APOBEC-1 Complementation Factor, a Novel RNA-Binding Protein Involved in the Editing of Apolipoprotein B mRNA Mol. Cell. Biol. 2000, 20, 1846-1854 10.1128/MCB.20.5.1846-1854.2000
208. Navaratnam, N.; Morrison, J. R.; Bhattacharya, S.; Patel, D.; Funahashi, T.; Giannoni, F.; Teng, B. B.; Davidson, N. O.; Scott, J. The P27 Catalytic Subunit of the Apolipoprotein B mRNA Editing Enzyme Is a Cytidine Deaminase J. Biol. Chem. 1993, 268, 20709-20712
209. Rosenberg, B. R.; Hamilton, C. E.; Mwangi, M. M.; Dewell, S.; Papavasiliou, F. N. Transcriptome-Wide Sequencing Reveals Numerous APOBEC1 mRNA-Editing Targets in Transcript 3′ UTRs Nat. Struct. Mol. Biol. 2011, 18, 230-236 10.1038/nsmb.1975
210. Skuse, G. R.; Cappione, A. J.; Sowden, M.; Metheny, L. J.; Smith, H. C. The Neurofibromatosis Type I Messenger RNA Undergoes Base-Modification RNA Editing Nucleic Acids Res. 1996, 24, 478-485 10.1093/nar/24.3.478
211. Yamanaka, S.; Poksay, K. S.; Arnold, K. S.; Innerarity, T. L. A Novel Translational Repressor mRNA Is Edited Extensively in Livers Containing Tumors Caused by the Transgene Expression of the ApoB mRNA-Editing Enzyme Genes Dev. 1997, 11, 321-333 10.1101/gad.11.3.321
212. Yamanaka, S.; Balestra, M. E.; Ferrell, L. D.; Fan, J.; Arnold, K. S.; Taylor, S.; Taylor, J. M.; Innerarity, T. L. Apolipoprotein B mRNA-Editing Protein Induces Hepatocellular Carcinoma and Dysplasia in Transgenic Animals Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 8483-8487 10.1073/pnas.92.18.8483
213. Saraconi, G.; Severi, F.; Sala, C.; Mattiuz, G.; Conticello, S. G. The RNA Editing Enzyme APOBEC1 Induces Somatic Mutations and a Compatible Mutational Signature Is Present in Esophageal Adenocarcinomas Genome Biol. 2014, 15, 417 10.1186/s13059-014-0417-z
214. Mariani, R.; Chen, D.; Schrofelbauer, B.; Navarro, F.; Konig, R.; Bollman, B.; Munk, C.; Nymark-McMahon, H.; Landau, N. R. Species-Specific Exclusion of APOBEC3G from HIV-1 Virions by Vif Cell 2003, 114, 21-31 10.1016/S0092-8674(03)00515-4
215. Refsland, E. W.; Stenglein, M. D.; Shindo, K.; Albin, J. S.; Brown, W. L.; Harris, R. S. Quantitative Profiling of the Full APOBEC3 mRNA Repertoire in Lymphocytes and Tissues: Implications for HIV-1 Restriction Nucleic Acids Res. 2010, 38, 4274-4284 10.1093/nar/gkq174
216. Koning, F. A.; Newman, E. N.; Kim, E. Y.; Kunstman, K. J.; Wolinsky, S. M.; Malim, M. H. Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets J. Virol. 2009, 83, 9474-9485 10.1128/JVI.01089-09
217. Peng, G.; Lei, K. J.; Jin, W.; Greenwell-Wild, T.; Wahl, S. M. Induction of APOBEC3 Family Proteins, a Defensive Maneuver Underlying Interferon-Induced Anti-HIV-1 Activity J. Exp. Med. 2006, 203, 41-46 10.1084/jem.20051512
218. Chen, K.; Huang, J.; Zhang, C.; Huang, S.; Nunnari, G.; Wang, F. X.; Tong, X.; Gao, L.; Nikisher, K.; Zhang, H. Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary Cd4 T Cells J. Virol. 2006, 80, 7645-7657 10.1128/JVI.00206-06
219. Wang, F. X.; Huang, J.; Zhang, H.; Ma, X.; Zhang, H. APOBEC3G Upregulation by Alpha Interferon Restricts Human Immunodeficiency Virus Type 1 Infection in Human Peripheral Plasmacytoid Dendritic Cells J. Gen. Virol. 2008, 89, 722-730 10.1099/vir.0.83530-0
220. Stopak, K. S.; Chiu, Y. L.; Kropp, J.; Grant, R. M.; Greene, W. C. Distinct Patterns of Cytokine Regulation of APOBEC3G Expression and Activity in Primary Lymphocytes, Macrophages, and Dendritic Cells J. Biol. Chem. 2007, 282, 3539-3546 10.1074/jbc.M610138200
221. Argyris, E. G.; Acheampong, E.; Wang, F.; Huang, J.; Chen, K.; Mukhtar, M.; Zhang, H. The Interferon-Induced Expression of APOBEC3G in Human Blood-Brain Barrier Exerts a Potent Intrinsic Immunity to Block HIV-1 Entry to Central Nervous System Virology 2007, 367, 440-451 10.1016/j.virol.2007.06.010
222. Tanaka, Y.; Marusawa, H.; Seno, H.; Matsumoto, Y.; Ueda, Y.; Kodama, Y.; Endo, Y.; Yamauchi, J.; Matsumoto, T.; Takaori-Kondo, A. et al. Anti-Viral Protein APOBEC3G Is Induced by Interferon-Alpha Stimulation in Human Hepatocytes Biochem. Biophys. Res. Commun. 2006, 341, 314-319 10.1016/j.bbrc.2005.12.192
223. Bonvin, M.; Achermann, F.; Greeve, I.; Stroka, D.; Keogh, A.; Inderbitzin, D.; Candinas, D.; Sommer, P.; Wain-Hobson, S.; Vartanian, J. P. et al. Interferon-Inducible Expression of APOBEC3 Editing Enzymes in Human Hepatocytes and Inhibition of Hepatitis B Virus Replication Hepatology 2006, 43, 1364-1374 10.1002/hep.21187
224. Lucifora, J.; Xia, Y.; Reisinger, F.; Zhang, K.; Stadler, D.; Cheng, X.; Sprinzl, M. F.; Koppensteiner, H.; Makowska, Z.; Volz, T. et al. Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus Cccdna Science 2014, 343, 1221-1228 10.1126/science.1243462
225. Wang, Z.; Wakae, K.; Kitamura, K.; Aoyama, S.; Liu, G.; Koura, M.; Monjurul, A. M.; Kukimoto, I.; Muramatsu, M. APOBEC3 Deaminases Induce Hypermutation in Human Papillomavirus 16 DNA Upon Beta Interferon Stimulation J. Virol. 2014, 88, 1308-1317 10.1128/JVI.03091-13
226. Madsen, P.; Anant, S.; Rasmussen, H. H.; Gromov, P.; Vorum, H.; Dumanski, J. P.; Tommerup, N.; Collins, J. E.; Wright, C. L.; Dunham, I. et al. Psoriasis Upregulated Phorbolin-1 Shares Structural but Not Functional Similarity to the mRNA-Editing Protein APOBEC-1 J. Invest. Dermatol. 1999, 113, 162-169 10.1046/j.1523-1747.1999.00682.x
227. Rasmussen, H. H.; Celis, J. E. Evidence for an Altered Protein Kinase C (Pkc) Signaling Pathway in Psoriasis J. Invest. Dermatol. 1993, 101, 560-566 10.1111/1523-1747.ep12365986
228. Rose, K. M.; Marin, M.; Kozak, S. L.; Kabat, D. Transcriptional Regulation of APOBEC3G, a Cytidine Deaminase That Hypermutates Human Immunodeficiency Virus J. Biol. Chem. 2004, 279, 41744-41749 10.1074/jbc.M406760200
229. Leonard, B.; McCann, J. L.; Starrett, G. J.; Kosyakovsky, L.; Luengas, E. M.; Molan, A. M.; Burns, M. B.; McDougle, R. M.; Parker, P. J.; Brown, W. L. et al. The Pkc/Nf-Kappab Signaling Pathway Induces APOBEC3B Expression in Multiple Human Cancers Cancer Res. 2015, 75, 4538-4547 10.1158/0008-5472.CAN-15-2171-T
230. Medzhitov, R. Recognition of Microorganisms and Activation of the Immune Response Nature 2007, 449, 819-826 10.1038/nature06246
231. Burckstummer, T.; Baumann, C.; Bluml, S.; Dixit, E.; Durnberger, G.; Jahn, H.; Planyavsky, M.; Bilban, M.; Colinge, J.; Bennett, K. L. et al. An Orthogonal Proteomic-Genomic Screen Identifies Aim2 as a Cytoplasmic DNA Sensor for the Inflammasome Nat. Immunol. 2009, 10, 266-272 10.1038/ni.1702
232. Sadler, A. J.; Williams, B. R. Interferon-Inducible Antiviral Effectors Nat. Rev. Immunol. 2008, 8, 559-568 10.1038/nri2314
233. Takaoka, A.; Wang, Z.; Choi, M. K.; Yanai, H.; Negishi, H.; Ban, T.; Lu, Y.; Miyagishi, M.; Kodama, T.; Honda, K. et al. Dai (Dlm-1/Zbp1) Is a Cytosolic DNA Sensor and an Activator of Innate Immune Response Nature 2007, 448, 501-505 10.1038/nature06013
234. Barber, G. N. Cytoplasmic DNA Innate Immune Pathways Immunol. Rev. 2011, 243, 99-108 10.1111/j.1600-065X.2011.01051.x
235. Barber, G. N. Sting: Infection, Inflammation and Cancer Nat. Rev. Immunol. 2015, 15, 760-770 10.1038/nri3921
236. Radoshevich, L.; Dussurget, O. Cytosolic Innate Immune Sensing and Signaling Upon Infection Front. Microbiol. 2016, 7, 313 10.3389/fmicb.2016.00313
237. Stenglein, M. D.; Burns, M. B.; Li, M.; Lengyel, J.; Harris, R. S. APOBEC3 Proteins Mediate the Clearance of Foreign DNA from Human Cells Nat. Struct. Mol. Biol. 2010, 17, 222-229 10.1038/nsmb.1744
238. Land, A. M.; Law, E. K.; Carpenter, M. A.; Lackey, L.; Brown, W. L.; Harris, R. S. Endogenous APOBEC3A DNA Cytosine Deaminase Is Cytoplasmic and Nongenotoxic J. Biol. Chem. 2013, 288, 17253-17260 10.1074/jbc.M113.458661
239. Messina, J. P.; Gilkeson, G. S.; Pisetsky, D. S. The Influence of DNA Structure on the in Vitro Stimulation of Murine Lymphocytes by Natural and Synthetic Polynucleotide Antigens Cell. Immunol. 1993, 147, 148-157 10.1006/cimm.1993.1055
240. Carpenter, M. A.; Li, M.; Rathore, A.; Lackey, L.; Law, E. K.; Land, A. M.; Leonard, B.; Shandilya, S. M.; Bohn, M. F.; Schiffer, C. A. et al. Methylcytosine and Normal Cytosine Deamination by the Foreign DNA Restriction Enzyme APOBEC3A J. Biol. Chem. 2012, 287, 34801-34808 10.1074/jbc.M112.385161
241. Suspene, R.; Aynaud, M. M.; Vartanian, J. P.; Wain-Hobson, S. Efficient Deamination of 5-Methylcytidine and 5-Substituted Cytidine Residues in DNA by Human APOBEC3A Cytidine Deaminase PLoS One 2013, 8, e63461 10.1371/journal.pone.0063461
242. Hoelzer, K.; Shackelton, L. A.; Parrish, C. R. Presence and Role of Cytosine Methylation in DNA Viruses of Animals Nucleic Acids Res. 2008, 36, 2825-2837 10.1093/nar/gkn121
243. Vieira, V. C.; Soares, M. A. The Role of Cytidine Deaminases on Innate Immune Responses against Human Viral Infections BioMed Res. Int. 2013, 2013, 683095 10.1155/2013/683095
244. Sheehy, A. M.; Gaddis, N. C.; Choi, J. D.; Malim, M. H. Isolation of a Human Gene That Inhibits HIV-1 Infection and Is Suppressed by the Viral Vif Protein Nature 2002, 418, 646-650 10.1038/nature00939
245. Desimmie, B. A.; Delviks-Frankenberrry, K. A.; Burdick, R. C.; Qi, D.; Izumi, T.; Pathak, V. K. Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them All J. Mol. Biol. 2014, 426, 1220-1245 10.1016/j.jmb.2013.10.033
246. Harris, R. S.; Dudley, J. P. APOBECs and Virus Restriction Virology 2015, 479-480, 131-145 10.1016/j.virol.2015.03.012
247. Moris, A.; Murray, S.; Cardinaud, S. AID and APOBECs Span the Gap between Innate and Adaptive Immunity Front. Microbiol. 2014, 5, 534 10.3389/fmicb.2014.00534
248. Mangeat, B.; Turelli, P.; Caron, G.; Friedli, M.; Perrin, L.; Trono, D. Broad Antiretroviral Defence by Human APOBEC3G through Lethal Editing of Nascent Reverse Transcripts Nature 2003, 424, 99-103 10.1038/nature01709
249. Zhang, H.; Yang, B.; Pomerantz, R. J.; Zhang, C.; Arunachalam, S. C.; Gao, L. The Cytidine Deaminase Cem15 Induces Hypermutation in Newly Synthesized HIV-1 DNA Nature 2003, 424, 94-98 10.1038/nature01707
250. Goila-Gaur, R.; Strebel, K. HIV-1 Vif, APOBEC, and Intrinsic Immunity Retrovirology 2008, 5, 51 10.1186/1742-4690-5-51
251. Krokan, H. E.; Drablos, F.; Slupphaug, G. Uracil in DNA - Occurrence, Consequences and Repair Oncogene 2002, 21, 8935-8948 10.1038/sj.onc.1205996
252. Conticello, S. G.; Harris, R. S.; Neuberger, M. S. The Vif Protein of HIV Triggers Degradation of the Human Antiretroviral DNA Deaminase APOBEC3G Curr. Biol. 2003, 13, 2009-2013 10.1016/j.cub.2003.10.034
253. Sheehy, A. M.; Gaddis, N. C.; Malim, M. H. The Antiretroviral Enzyme APOBEC3G Is Degraded by the Proteasome in Response to HIV-1 Vif Nat. Med. 2003, 9, 1404-1407 10.1038/nm945
254. Yu, X.; Yu, Y.; Liu, B.; Luo, K.; Kong, W.; Mao, P.; Yu, X. F. Induction of APOBEC3G Ubiquitination and Degradation by an HIV-1 Vif-Cul5-Scf Complex Science 2003, 302, 1056-1060 10.1126/science.1089591
255. Aydin, H.; Taylor, M. W.; Lee, J. E. Structure-Guided Analysis of the Human APOBEC3-HIV Restrictome Structure 2014, 22, 668-684 10.1016/j.str.2014.02.011
256. Feng, Y.; Baig, T. T.; Love, R. P.; Chelico, L. Suppression of APOBEC3-Mediated Restriction of HIV-1 by Vif Front. Microbiol. 2014, 5, 450 10.3389/fmicb.2014.00450
257. Kim, D. Y. The Assembly of Vif Ubiquitin E3 Ligase for APOBEC3 Degradation Arch. Pharmacal Res. 2015, 38, 435-445 10.1007/s12272-014-0519-x
258. Salter, J. D.; Morales, G. A.; Smith, H. C. Structural Insights for HIV-1 Therapeutic Strategies Targeting Vif Trends Biochem. Sci. 2014, 39, 373-380 10.1016/j.tibs.2014.07.001
259. Hultquist, J. F.; Lengyel, J. A.; Refsland, E. W.; LaRue, R. S.; Lackey, L.; Brown, W. L.; Harris, R. S. Human and Rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H Demonstrate a Conserved Capacity to Restrict Vif-Deficient HIV-1 J. Virol. 2011, 85, 11220-11234 10.1128/JVI.05238-11
260. Sato, K.; Takeuchi, J. S.; Misawa, N.; Izumi, T.; Kobayashi, T.; Kimura, Y.; Iwami, S.; Takaori-Kondo, A.; Hu, W. S.; Aihara, K. et al. APOBEC3D and APOBEC3F Potently Promote HIV-1 Diversification and Evolution in Humanized Mouse Model PLoS Pathog. 2014, 10, e1004453 10.1371/journal.ppat.1004453
261. Berger, G.; Durand, S.; Fargier, G.; Nguyen, X. N.; Cordeil, S.; Bouaziz, S.; Muriaux, D.; Darlix, J. L.; Cimarelli, A. APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells PLoS Pathog. 2011, 7, e1002221 10.1371/journal.ppat.1002221
262. Doehle, B. P.; Schafer, A.; Cullen, B. R. Human APOBEC3B Is a Potent Inhibitor of HIV-1 Infectivity and Is Resistant to HIV-1 Vif Virology 2005, 339, 281-288 10.1016/j.virol.2005.06.005
263. Itaya, S.; Nakajima, T.; Kaur, G.; Terunuma, H.; Ohtani, H.; Mehra, N.; Kimura, A. No Evidence of an Association between the APOBEC3B Deletion Polymorphism and Susceptibility to HIV Infection and AIDs in Japanese and Indian Populations J. Infect. Dis. 2010, 202, 815-816 (author reply pp 816-817). 10.1086/655227
264. Yu, Q.; Chen, D.; Konig, R.; Mariani, R.; Unutmaz, D.; Landau, N. R. APOBEC3B and APOBEC3C Are Potent Inhibitors of Simian Immunodeficiency Virus Replication J. Biol. Chem. 2004, 279, 53379-53386 10.1074/jbc.M408802200
265. Holmes, R. K.; Koning, F. A.; Bishop, K. N.; Malim, M. H. APOBEC3F Can Inhibit the Accumulation of HIV-1 Reverse Transcription Products in the Absence of Hypermutation. Comparisons with APOBEC3G J. Biol. Chem. 2007, 282, 2587-2595 10.1074/jbc.M607298200
266. Iwatani, Y.; Chan, D. S.; Wang, F.; Maynard, K. S.; Sugiura, W.; Gronenborn, A. M.; Rouzina, I.; Williams, M. C.; Musier-Forsyth, K.; Levin, J. G. Deaminase-Independent Inhibition of HIV-1 Reverse Transcription by APOBEC3G Nucleic Acids Res. 2007, 35, 7096-7108 10.1093/nar/gkm750
267. Bishop, K. N.; Verma, M.; Kim, E. Y.; Wolinsky, S. M.; Malim, M. H. APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts PLoS Pathog. 2008, 4, e1000231 10.1371/journal.ppat.1000231
268. Gillick, K.; Pollpeter, D.; Phalora, P.; Kim, E. Y.; Wolinsky, S. M.; Malim, M. H. Suppression of HIV-1 Infection by APOBEC3 Proteins in Primary Human Cd4(+) T Cells Is Associated with Inhibition of Processive Reverse Transcription as Well as Excessive Cytidine Deamination J. Virol. 2013, 87, 1508-1517 10.1128/JVI.02587-12
269. Sasada, A.; Takaori-Kondo, A.; Shirakawa, K.; Kobayashi, M.; Abudu, A.; Hishizawa, M.; Imada, K.; Tanaka, Y.; Uchiyama, T. APOBEC3G Targets Human T-Cell Leukemia Virus Type 1 Retrovirology 2005, 2, 32 10.1186/1742-4690-2-32
270. Fan, J.; Ma, G.; Nosaka, K.; Tanabe, J.; Satou, Y.; Koito, A.; Wain-Hobson, S.; Vartanian, J. P.; Matsuoka, M. APOBEC3G Generates Nonsense Mutations in Human T-Cell Leukemia Virus Type 1 Proviral Genomes in Vivo J. Virol. 2010, 84, 7278-7287 10.1128/JVI.02239-09
271. Ooms, M.; Krikoni, A.; Kress, A. K.; Simon, V.; Munk, C. APOBEC3A, APOBEC3B, and APOBEC3H Haplotype 2 Restrict Human T-Lymphotropic Virus Type 1 J. Virol. 2012, 86, 6097-6108 10.1128/JVI.06570-11
272. Delebecque, F.; Suspene, R.; Calattini, S.; Casartelli, N.; Saib, A.; Froment, A.; Wain-Hobson, S.; Gessain, A.; Vartanian, J. P.; Schwartz, O. Restriction of Foamy Viruses by APOBEC Cytidine Deaminases J. Virol. 2006, 80, 605-614 10.1128/JVI.80.2.605-614.2006
273. Derse, D.; Hill, S. A.; Princler, G.; Lloyd, P.; Heidecker, G. Resistance of Human T Cell Leukemia Virus Type 1 to APOBEC3G Restriction Is Mediated by Elements in Nucleocapsid Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 2915-2920 10.1073/pnas.0609444104
274. Oguariri, R. M.; Dai, L.; Adelsberger, J. W.; Rupert, A.; Stevens, R.; Yang, J.; Huang, D.; Lempicki, R. A.; Zhou, M.; Baseler, M. W. et al. Interleukin-2 Inhibits HIV-1 Replication in Some Human T Cell Lymphotrophic Virus-1-Infected Cell Lines Via the Induction and Incorporation of APOBEC3G into the Virion J. Biol. Chem. 2013, 288, 17812-17822 10.1074/jbc.M113.468975
275. Ohsugi, T.; Koito, A. Human T Cell Leukemia Virus Type I Is Resistant to the Antiviral Effects of APOBEC3 J. Virol. Methods 2007, 139, 93-96 10.1016/j.jviromet.2006.08.016
276. Russell, R. A.; Wiegand, H. L.; Moore, M. D.; Schafer, A.; McClure, M. O.; Cullen, B. R. Foamy Virus Bet Proteins Function as Novel Inhibitors of the APOBEC3 Family of Innate Antiretroviral Defense Factors J. Virol. 2005, 79, 8724-8731 10.1128/JVI.79.14.8724-8731.2005
277. Janahi, E. M.; McGarvey, M. J. The Inhibition of Hepatitis B Virus by APOBEC Cytidine Deaminases J. Viral Hepat 2013, 20, 821-828 10.1111/jvh.12192
278. Chen, H.; Lilley, C. E.; Yu, Q.; Lee, D. V.; Chou, J.; Narvaiza, I.; Landau, N. R.; Weitzman, M. D. APOBEC3A Is a Potent Inhibitor of Adeno-Associated Virus and Retrotransposons Curr. Biol. 2006, 16, 480-485 10.1016/j.cub.2006.01.031
279. Narvaiza, I.; Linfesty, D. C.; Greener, B. N.; Hakata, Y.; Pintel, D. J.; Logue, E.; Landau, N. R.; Weitzman, M. D. Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase PLoS Pathog. 2009, 5, e1000439 10.1371/journal.ppat.1000439
280. Suspene, R.; Guetard, D.; Henry, M.; Sommer, P.; Wain-Hobson, S.; Vartanian, J. P. 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. 2005, 102, 8321-8326 10.1073/pnas.0408223102
281. He, X.; Li, J.; Wu, J.; Zhang, M.; Gao, P. Associations between Activation-Induced Cytidine Deaminase/Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide-Like Cytidine Deaminase Expression, Hepatitis B Virus (Hbv) Replication and Hbv-Associated Liver Disease (Review) Mol. Med. Rep. 2015, 12, 6405-6414 10.3892/mmr.2015.4312
282. Vieira, V. C.; Leonard, B.; White, E. A.; Starrett, G. J.; Temiz, N. A.; Lorenz, L. D.; Lee, D.; Soares, M. A.; Lambert, P. F.; Howley, P. M. Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B mBio 2014, 5, e02234-14 10.1128/mBio.02234-14
283. Vartanian, J. P.; Guetard, D.; Henry, M.; Wain-Hobson, S. Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous Lesions Science 2008, 320, 230-233 10.1126/science.1153201
284. Suspene, R.; Aynaud, M. M.; Koch, S.; Pasdeloup, D.; Labetoulle, M.; Gaertner, B.; Vartanian, J. P.; Meyerhans, A.; Wain-Hobson, S. Genetic Editing of Herpes Simplex Virus 1 and Epstein-Barr Herpesvirus Genomes by Human APOBEC3 Cytidine Deaminases in Culture and in Vivo J. Virol. 2011, 85, 7594-7602 10.1128/JVI.00290-11
285. Minkah, N.; Macaluso, M.; Oldenburg, D. G.; Paden, C. R.; White, D. W.; McBride, K. M.; Krug, L. T. Absence of the Uracil DNA Glycosylase of Murine Gammaherpesvirus 68 Impairs Replication and Delays the Establishment of Latency in Vivo J. Virol. 2015, 89, 3366-3379 10.1128/JVI.03111-14
286. Pyles, R. B.; Thompson, R. L. Evidence That the Herpes Simplex Virus Type 1 Uracil DNA Glycosylase Is Required for Efficient Viral Replication and Latency in the Murine Nervous System J. Virol. 1994, 68, 4963-4972
287. Su, M. T.; Liu, I. H.; Wu, C. W.; Chang, S. M.; Tsai, C. H.; Yang, P. W.; Chuang, Y. C.; Lee, C. P.; Chen, M. R. Uracil DNA Glycosylase BKRF3 Contributes to Epstein-Barr Virus DNA Replication through Physical Interactions with Proteins in Viral DNA Replication Complex J. Virol. 2014, 88, 8883-8899 10.1128/JVI.00950-14
288. Suspene, R.; Henry, M.; Guillot, S.; Wain-Hobson, S.; Vartanian, J. P. Recovery of APOBEC3-Edited Human Immunodeficiency Virus G- > A Hypermutants by Differential DNA Denaturation PCR J. Gen. Virol. 2005, 86, 125-129 10.1099/vir.0.80426-0
289. Suspene, R.; Caval, V.; Henry, M.; Bouzidi, M. S.; Wain-Hobson, S.; Vartanian, J. P. Erroneous Identification of APOBEC3-Edited Chromosomal DNA in Cancer Genomics Br. J. Cancer 2014, 110, 2615-2622 10.1038/bjc.2014.176
290. Bogerd, H. P.; Wiegand, H. L.; Hulme, A. E.; Garcia-Perez, J. L.; O'Shea, K. S.; Moran, J. V.; Cullen, B. R. Cellular Inhibitors of Long Interspersed Element 1 and Alu Retrotransposition Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 8780-8785 10.1073/pnas.0603313103
291. Muckenfuss, H.; Hamdorf, M.; Held, U.; Perkovic, M.; Lower, J.; Cichutek, K.; Flory, E.; Schumann, G. G.; Munk, C. APOBEC3 Proteins Inhibit Human Line-1 Retrotransposition J. Biol. Chem. 2006, 281, 22161-22172 10.1074/jbc.M601716200
292. OhAinle, M.; Kerns, J. A.; Li, M. M.; Malik, H. S.; Emerman, M. Antiretroelement Activity of APOBEC3H Was Lost Twice in Recent Human Evolution Cell Host Microbe 2008, 4, 249-259 10.1016/j.chom.2008.07.005
293. Richardson, S. R.; Narvaiza, I.; Planegger, R. A.; Weitzman, M. D.; Moran, J. V. APOBEC3A Deaminates Transiently Exposed Single-Strand DNA During Line-1 Retrotransposition eLife 2014, 3, e02008 10.7554/eLife.02008
294. Horn, A. V.; Klawitter, S.; Held, U.; Berger, A.; Vasudevan, A. A.; Bock, A.; Hofmann, H.; Hanschmann, K. M.; Trosemeier, J. H.; Flory, E. et al. Human Line-1 Restriction by APOBEC3C Is Deaminase Independent and Mediated by an ORF1p Interaction That Affects Line Reverse Transcriptase Activity Nucleic Acids Res. 2014, 42, 396-416 10.1093/nar/gkt898
295. Stenglein, M. D.; Harris, R. S. APOBEC3B and APOBEC3F Inhibit L1 Retrotransposition by a DNA Deamination-Independent Mechanism J. Biol. Chem. 2006, 281, 16837-16841 10.1074/jbc.M602367200
296. Holmes, R. K.; Malim, M. H.; Bishop, K. N. APOBEC-Mediated Viral Restriction: Not Simply Editing? Trends Biochem. Sci. 2007, 32, 118-128 10.1016/j.tibs.2007.01.004
297. Koyama, T.; Arias, J. F.; Iwabu, Y.; Yokoyama, M.; Fujita, H.; Sato, H.; Tokunaga, K. APOBEC3G Oligomerization Is Associated with the Inhibition of Both Alu and Line-1 Retrotransposition PLoS One 2013, 8, e84228 10.1371/journal.pone.0084228
298. Dutko, J. A.; Schafer, A.; Kenny, A. E.; Cullen, B. R.; Curcio, M. J. Inhibition of a Yeast LTR Retrotransposon by Human APOBEC3 Cytidine Deaminases Curr. Biol. 2005, 15, 661-666 10.1016/j.cub.2005.02.051
299. Esnault, C.; Heidmann, O.; Delebecque, F.; Dewannieux, M.; Ribet, D.; Hance, A. J.; Heidmann, T.; Schwartz, O. APOBEC3G Cytidine Deaminase Inhibits Retrotransposition of Endogenous Retroviruses Nature 2005, 433, 430-433 10.1038/nature03238
300. Duggal, N. K.; Malik, H. S.; Emerman, M. The Breadth of Antiviral Activity of APOBEC3DE in Chimpanzees Has Been Driven by Positive Selection J. Virol. 2011, 85, 11361-11371 10.1128/JVI.05046-11
301. Bannert, N.; Kurth, R. Retroelements and the Human Genome: New Perspectives on an Old Relation Proc. Natl. Acad. Sci. U. S. A. 2004, 101 (Suppl 2) 14572-14579 10.1073/pnas.0404838101
302. Anwar, F.; Davenport, M. P.; Ebrahimi, D. Footprint of APOBEC3 on the Genome of Human Retroelements J. Virol. 2013, 87, 8195-8204 10.1128/JVI.00298-13
303. Bailey, J. A.; Liu, G.; Eichler, E. E. An Alu Transposition Model for the Origin and Expansion of Human Segmental Duplications Am. J. Hum. Genet. 2003, 73, 823-834 10.1086/378594
304. Kim, T. M.; Hong, S. J.; Rhyu, M. G. Periodic Explosive Expansion of Human Retroelements Associated with the Evolution of the Hominoid Primate J. Korean Med. Sci. 2004, 19, 177-185 10.3346/jkms.2004.19.2.177
305. Marques, A. C.; Dupanloup, I.; Vinckenbosch, N.; Reymond, A.; Kaessmann, H. Emergence of Young Human Genes after a Burst of Retroposition in Primates PLoS Biol. 2005, 3, e357 10.1371/journal.pbio.0030357
306. Pasqualucci, L.; Migliazza, A.; Fracchiolla, N.; William, C.; Neri, A.; Baldini, L.; Chaganti, R. S.; Klein, U.; Kuppers, R.; Rajewsky, K. et al. Bcl-6 Mutations in Normal Germinal Center B Cells: Evidence of Somatic Hypermutation Acting Outside Ig Loci Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 11816-11821 10.1073/pnas.95.20.11816
307. Shen, H. M.; Peters, A.; Baron, B.; Zhu, X.; Storb, U. Mutation of Bcl-6 Gene in Normal B Cells by the Process of Somatic Hypermutation of Ig Genes Science 1998, 280, 1750-1752 10.1126/science.280.5370.1750
308. Nik-Zainal, S.; Alexandrov, L. B.; Wedge, D. C.; Van Loo, P.; Greenman, C. D.; Raine, K.; Jones, D.; Hinton, J.; Marshall, J.; Stebbings, L. A. et al. Mutational Processes Molding the Genomes of 21 Breast Cancers Cell 2012, 149, 979-993 10.1016/j.cell.2012.04.024
309. Roberts, S. A.; Lawrence, M. S.; Klimczak, L. J.; Grimm, S. A.; Fargo, D.; Stojanov, P.; Kiezun, A.; Kryukov, G. V.; Carter, S. L.; Saksena, G. et al. An APOBEC Cytidine Deaminase Mutagenesis Pattern Is Widespread in Human Cancers Nat. Genet. 2013, 45, 970-976 10.1038/ng.2702
310. Roberts, S. A.; Sterling, J.; Thompson, C.; Harris, S.; Mav, D.; Shah, R.; Klimczak, L. J.; Kryukov, G. V.; Malc, E.; Mieczkowski, P. A. et al. Clustered Mutations in Yeast and in Human Cancers Can Arise from Damaged Long Single-Strand DNA Regions Mol. Cell 2012, 46, 424-435 10.1016/j.molcel.2012.03.030
311. Alexandrov, L. B.; Nik-Zainal, S.; Wedge, D. C.; Aparicio, S. A.; Behjati, S.; Biankin, A. V.; Bignell, G. R.; Bolli, N.; Borg, A.; Borresen-Dale, A. L. et al. Signatures of Mutational Processes in Human Cancer Nature 2013, 500, 415-421 10.1038/nature12477
312. Burns, M. B.; Temiz, N. A.; Harris, R. S. Evidence for APOBEC3B Mutagenesis in Multiple Human Cancers Nat. Genet. 2013, 45, 977-983 10.1038/ng.2701
313. Burns, M. B.; Lackey, L.; Carpenter, M. A.; Rathore, A.; Land, A. M.; Leonard, B.; Refsland, E. W.; Kotandeniya, D.; Tretyakova, N.; Nikas, J. B. et al. APOBEC3B Is an Enzymatic Source of Mutation in Breast Cancer Nature 2013, 494, 366-370 10.1038/nature11881
314. Chan, K.; Roberts, S. A.; Klimczak, L. J.; Sterling, J. F.; Saini, N.; Malc, E. P.; Kim, J.; Kwiatkowski, D. J.; Fargo, D. C.; Mieczkowski, P. A. et al. An APOBEC3A Hypermutation Signature Is Distinguishable from the Signature of Background Mutagenesis by APOBEC3B in Human Cancers Nat. Genet. 2015, 47, 1067-1072 10.1038/ng.3378
315. Taylor, B. J.; Nik-Zainal, S.; Wu, Y. L.; Stebbings, L. A.; Raine, K.; Campbell, P. J.; Rada, C.; Stratton, M. R.; Neuberger, M. S. DNA Deaminases Induce Break-Associated Mutation Showers with Implication of APOBEC3B and 3A in Breast Cancer Kataegis eLife 2013, 2, e00534 10.7554/eLife.00534
316. Kuong, K. J.; Loeb, L. A. APOBEC3B Mutagenesis in Cancer Nat. Genet. 2013, 45, 964-965 10.1038/ng.2736
317. Henderson, S.; Chakravarthy, A.; Su, X.; Boshoff, C.; Fenton, T. R. APOBEC-Mediated Cytosine Deamination Links Pik3Ca Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development Cell Rep. 2014, 7, 1833-1841 10.1016/j.celrep.2014.05.012
318. Gabelli, S. B.; Echeverria, I.; Alexander, M.; Duong-Ly, K. C.; Chaves-Moreira, D.; Brower, E. T.; Vogelstein, B.; Amzel, L. M. Activation of Pi3kalpha by Physiological Effectors and by Oncogenic Mutations: Structural and Dynamic Effects Biophys. Rev. 2014, 6, 89-95 10.1007/s12551-013-0131-1
319. Chelico, L.; Pham, P.; Goodman, M. F. Stochastic Properties of Processive Cytidine DNA Deaminases AID and APOBEC3G Philos. Trans. R. Soc., B 2009, 364, 583-593 10.1098/rstb.2008.0195
320. Kazanov, M. D.; Roberts, S. A.; Polak, P.; Stamatoyannopoulos, J.; Klimczak, L. J.; Gordenin, D. A.; Sunyaev, S. R. APOBEC-Induced Cancer Mutations Are Uniquely Enriched in Early-Replicating, Gene-Dense, and Active Chromatin Regions Cell Rep. 2015, 13, 1103-1109 10.1016/j.celrep.2015.09.077
321. Green, A. M.; Landry, S.; Budagyan, K.; Avgousti, D. C.; Shalhout, S.; Bhagwat, A. S.; Weitzman, M. D. APOBEC3A Damages the Cellular Genome During DNA Replication Cell Cycle 2016, 15, 998-1008 10.1080/15384101.2016.1152426
322. Chan, K.; Gordenin, D. A. Clusters of Multiple Mutations: Incidence and Molecular Mechanisms Annu. Rev. Genet. 2015, 49, 243-267 10.1146/annurev-genet-112414-054714
323. Haradhvala, N. J.; Polak, P.; Stojanov, P.; Covington, K. R.; Shinbrot, E.; Hess, J. M.; Rheinbay, E.; Kim, J.; Maruvka, Y. E.; Braunstein, L. Z. et al. Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair Cell 2016, 164, 538-549 10.1016/j.cell.2015.12.050
324. Seplyarskiy, V. B.; Soldatov, R. A.; Popadin, K. Y.; Antonarakis, S. E.; Bazykin, G. A.; Nikolaev, S. I. APOBEC-Induced Mutations in Human Cancers Are Strongly Enriched on the Lagging DNA Strand During Replication Genome Res. 2016, 26, 174-182 10.1101/gr.197046.115
325. Langston, L. D.; O'Donnell, M. DNA Replication: Keep Moving and Don't Mind the Gap Mol. Cell 2006, 23, 155-160 10.1016/j.molcel.2006.05.034
326. Hoopes, J. I.; Cortez, L. M.; Mertz, T. M.; Malc, E. P.; Mieczkowski, P. A.; Roberts, S. A. APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template During DNA Replication Cell Rep. 2016, 14, 1273-1282 10.1016/j.celrep.2016.01.021
327. Bhagwat, A. S.; Hao, W.; Townes, J. P.; Lee, H.; Tang, H.; Foster, P. L. Strand-Biased Cytosine Deamination at the Replication Fork Causes Cytosine to Thymine Mutations in Escherichia Coli Proc. Natl. Acad. Sci. U. S. A. 2016, 113, 2176-2181 10.1073/pnas.1522325113
328. Chan, K.; Sterling, J. F.; Roberts, S. A.; Bhagwat, A. S.; Resnick, M. A.; Gordenin, D. A. Base Damage within Single-Strand DNA Underlies in Vivo Hypermutability Induced by a Ubiquitous Environmental Agent PLoS Genet. 2012, 8, e1003149 10.1371/journal.pgen.1003149
329. Lada, A. G.; Kliver, S. F.; Dhar, A.; Polev, D. E.; Masharsky, A. E.; Rogozin, I. B.; Pavlov, Y. I. Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-Distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes PLoS Genet. 2015, 11, e1005217 10.1371/journal.pgen.1005217
330. Lada, A. G.; Stepchenkova, E. I.; Waisertreiger, I. S.; Noskov, V. N.; Dhar, A.; Eudy, J. D.; Boissy, R. J.; Hirano, M.; Rogozin, I. B.; Pavlov, Y. I. Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase PLoS Genet. 2013, 9, e1003736 10.1371/journal.pgen.1003736
331. Beletskii, A.; Bhagwat, A. S. Transcription-Induced Mutations: Increase in C to T Mutations in the Nontranscribed Strand During Transcription in Escherichia Coli Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 13919-13924 10.1073/pnas.93.24.13919
332. Parkin, D. M. The Global Health Burden of Infection-Associated Cancers in the Year 2002 Int. J. Cancer 2006, 118, 3030-3044 10.1002/ijc.21731
333. Butel, J. S. Viral Carcinogenesis: Revelation of Molecular Mechanisms and Etiology of Human Disease Carcinogenesis 2000, 21, 405-426 10.1093/carcin/21.3.405
334. Sarid, R.; Gao, S. J. Viruses and Human Cancer: From Detection to Causality Cancer Lett. 2011, 305, 218-227 10.1016/j.canlet.2010.09.011
335. Read, S. A.; Douglas, M. W. Virus Induced Inflammation and Cancer Development Cancer Lett. 2014, 345, 174-181 10.1016/j.canlet.2013.07.030
336. Chai, E. Z.; Siveen, K. S.; Shanmugam, M. K.; Arfuso, F.; Sethi, G. Analysis of the Intricate Relationship between Chronic Inflammation and Cancer Biochem. J. 2015, 468, 1-15 10.1042/BJ20141337
337. Warren, C. J.; Xu, T.; Guo, K.; Griffin, L. M.; Westrich, J. A.; Lee, D.; Lambert, P. F.; Santiago, M. L.; Pyeon, D. APOBEC3A Functions as a Restriction Factor of Human Papillomavirus J. Virol. 2015, 89, 688-702 10.1128/JVI.02383-14
338. Deng, Y.; Du, Y.; Zhang, Q.; Han, X.; Cao, G. Human Cytidine Deaminases Facilitate Hepatitis B Virus Evolution and Link Inflammation and Hepatocellular Carcinoma Cancer Lett. 2014, 343, 161-171 10.1016/j.canlet.2013.09.041
339. Niavarani, A.; Currie, E.; Reyal, Y.; Anjos-Afonso, F.; Horswell, S.; Griessinger, E.; Luis Sardina, J.; Bonnet, D. APOBEC3A Is Implicated in a Novel Class of G-to-A mRNA Editing in WT1 Transcripts PLoS One 2015, 10, e0120089 10.1371/journal.pone.0120089
340. Zheng, S.; Vuong, B. Q.; Vaidyanathan, B.; Lin, J. Y.; Huang, F. T.; Chaudhuri, J. Non-Coding RNA Generated Following Lariat Debranching Mediates Targeting of AID to DNA Cell 2015, 161, 762-773 10.1016/j.cell.2015.03.020
341. Le, Q.; Maizels, N. Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID PLoS Genet. 2015, 11, e1005411 10.1371/journal.pgen.1005411