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Review

Aid and Apobec Deaminases: Balancing Dna Damage in Epigenetics and Immunity

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Pages 427-443 | Published online: 21 Oct 2014

References

  • Lindahl T . Instability and decay of the primary structure of DNA . Nature362 ( 6422 ), 709 – 715 ( 1993 ).
  • Friedberg EC . DNA Repair And Mutagenesis.American Society for Microbiology , WA, USA ( 2005 ).
  • Neuberger MS , HarrisRS , Di NoiaJ , Petersen-MahrtSK . Immunity through DNA deamination . Trends Biochem. Sci.28 ( 6 ), 305 – 312 ( 2003 ).
  • Petersen-Mahrt S . DNA deamination in immunity . Immunol Rev.203 , 80 – 97 ( 2005 ).
  • Powell LM , WallisSC , PeaseRJ , EdwardsYH , KnottTJ , ScottJ . A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine . Cell50 ( 6 ), 831 – 840 ( 1987 ).
  • Teng B , BurantCF , DavidsonNO . Molecular cloning of an apolipoprotein B messenger RNA editing protein . Science260 ( 5115 ), 1816 – 1819 ( 1993 ).
  • Harris RS , Petersen-MahrtSK , NeubergerMS . RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators . Mol. Cell10 ( 5 ), 1247 – 1253 ( 2002 ).
  • Petersen-Mahrt SK , HarrisRS , NeubergerMS . AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification . Nature418 ( 6893 ), 99 – 103 ( 2002 ).
  • Franchini DM , SchmitzKM , Petersen-MahrtSK . 5-Methylcytosine DNA demethylation: more than losing a methyl group . Annu. Rev. Genet.46 , 419 – 441 ( 2012 ).
  • Janeway CA Jr , MedzhitovR . Innate immune recognition . Annu. Rev. Immunol.20 , 197 – 216 ( 2002 ).
  • Di Noia JM , NeubergerMS . Molecular mechanisms of antibody somatic hypermutation . Annu. Rev. Biochem.76 , 1 – 22 ( 2007 ).
  • Alt FW , ZhangY , MengFL , GuoC , SchwerB . Mechanisms of programmed DNA lesions and genomic instability in the immune system . Cell152 ( 3 ), 417 – 429 ( 2013 ).
  • Peled JU , KuangFL , Iglesias-UsselMDet al. The biochemistry of somatic hypermutation . Annu. Rev. Immunol.26 , 481 – 511 ( 2008 ).
  • Stavnezer J , GuikemaJE , SchraderCE . Mechanism and regulation of class switch recombination . Annu. Rev. Immunol.26 , 261 – 292 ( 2008 ).
  • Daniel JA , NussenzweigA . The AID-induced DNA damage response in chromatin . Mol. Cell50 ( 3 ), 309 – 321 ( 2013 ).
  • Muramatsu M , SankaranandVS , AnantSet al. 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 ( 1999 ).
  • Muramatsu M , KinoshitaK , FagarasanS , YamadaS , ShinkaiY , HonjoT . Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme . Cell102 ( 5 ), 553 – 563 ( 2000 ).
  • Revy P , MutoT , LevyYet al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2) . Cell102 ( 5 ), 565 – 575 ( 2000 ).
  • Bransteitter R , PhamP , ScharffMD , GoodmanMF . Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase . Proc. Natl Acad. Sci. USA100 ( 7 ), 4102 – 4107 ( 2003 ).
  • Chaudhuri J , TianM , KhuongC , ChuaK , PinaudE , AltFW . Transcription-targeted DNA deamination by the AID antibody diversification enzyme . Nature422 ( 6933 ), 726 – 730 ( 2003 ).
  • Dickerson SK , MarketE , BesmerE , PapavasiliouFN . AID mediates hypermutation by deaminating single stranded DNA . J. Exp. Med.197 ( 10 ), 1291 – 1296 ( 2003 ).
  • Ramiro AR , StavropoulosP , JankovicM , NussenzweigMC . Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand . Nat. Immunol.4 ( 5 ), 452 – 456 ( 2003 ).
  • Sohail A , KlapaczJ , SamaranayakeM , UllahA , BhagwatAS . Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations . Nucleic Acids Res.31 ( 12 ), 2990 – 2994 ( 2003 ).
  • Martin A , ScharffMD . Somatic hypermutation of the AID transgene in B and non-B cells . Proc. Natl Acad. Sci. USA99 ( 19 ), 12304 – 12308 ( 2002 ).
  • Mayorov VI , RogozinIB , AdkisonLR , FrahmC , KunkelTA , PavlovYI . Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes . BMC Immunol.6 , 10 ( 2005 ).
  • Yoshikawa K , OkazakiIM , EtoTet al. AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts . Science296 ( 5575 ), 2033 – 2036 ( 2002 ).
  • Betz AG , RadaC , PannellR , MilsteinC , NeubergerMS . Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots . Proc. Natl Acad. Sci. USA90 ( 6 ), 2385 – 2388 ( 1993 ).
  • Golding GB , GearhartPJ , GlickmanBW . Patterns of somatic mutations in immunoglobulin variable genes . Genetics115 ( 1 ), 169 – 176 ( 1987 ).
  • Morgan HD , DeanW , CokerHA , ReikW , Petersen-MahrtSK . Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming . J. Biol Chem.279 ( 50 ), 52353 – 52360 ( 2004 ).
  • Rogozin IB , KolchanovNA . Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis . Biochim. Biophys. Acta1171 ( 1 ), 11 – 18 ( 1992 ).
  • Di Noia J , NeubergerMS . Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase . Nature419 ( 6902 ), 43 – 48 ( 2002 ).
  • Imai K , SlupphaugG , LeeWIet al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination . Nat. Immunol.4 ( 10 ), 1023 – 1028 ( 2003 ).
  • Rada C , WilliamsGT , NilsenH , BarnesDE , LindahlT , NeubergerMS . Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice . Curr. Biol.12 ( 20 ), 1748 – 1755 ( 2002 ).
  • Cascalho M , WongJ , SteinbergC , WablM . Mismatch repair co-opted by hypermutation . Science279 ( 5354 ), 1207 – 1210 ( 1998 ).
  • Frey S , BertocciB , DelbosF , QuintL , WeillJC , ReynaudCA . Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process . Immunity9 ( 1 ), 127 – 134 ( 1998 ).
  • Martomo SA , YangWW , GearhartPJ . A role for Msh6 but not Msh3 in somatic hypermutation and class switch recombination . J. Exp. Med.200 ( 1 ), 61 – 68 ( 2004 ).
  • Phung QH , WinterDB , CranstonAet al. Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein . J. Exp. Med.187 ( 11 ), 1745 – 1751 ( 1998 ).
  • Rada C , EhrensteinMR , NeubergerMS , MilsteinC . Hot spot focusing of somatic hypermutation in MSH2-deficient mice suggests two stages of mutational targeting . Immunity9 ( 1 ), 135 – 141 ( 1998 ).
  • Wiesendanger M , KneitzB , EdelmannW , ScharffMD . Somatic hypermutation in MutS homologue (MSH)3-, MSH6-, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern . J. Exp. Med.191 ( 3 ), 579 – 584 ( 2000 ).
  • Rada C , Di NoiaJM , NeubergerMS . Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation . Mol. Cell16 ( 2 ), 163 – 171 ( 2004 ).
  • Shen HM , TanakaA , BozekG , NicolaeD , StorbU . Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice . J. Immunol.177 ( 8 ), 5386 – 5392 ( 2006 ).
  • Schrader CE , GuikemaJE , LinehanEK , SelsingE , StavnezerJ . Activation-induced cytidine deaminase-dependent DNA breaks in class switch recombination occur during G1 phase of the cell cycle and depend upon mismatch repair . J. Immunol.179 ( 9 ), 6064 – 6071 ( 2007 ).
  • Han L , MasaniS , YuK . Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination . Proc. Natl Acad. Sci. USA108 ( 28 ), 11584 – 11589 ( 2011 ).
  • Schmitz KM , Petersen-MahrtSK . AIDing the immune system-DIAbolic in cancer . Semin. Immunol.24 ( 4 ), 241 – 245 ( 2012 ).
  • Vuong BQ , LeeM , KabirSet al. Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination . Nat. Immunol.10 ( 4 ), 420 – 426 ( 2009 ).
  • Bardwell PD , MartinA , WongE , LiZ , EdelmannW , ScharffMD . Cutting edge: the G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination . J. Immunol.170 ( 4 ), 1620 – 1624 ( 2003 ).
  • Di Noia JM , RadaC , NeubergerMS . SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair . EMBO J.25 ( 3 ), 585 – 595 ( 2006 ).
  • Doseth B , EkreC , SlupphaugG , KrokanHE , KavliB . Strikingly different properties of uracil-DNA glycosylases UNG2 and SMUG1 may explain divergent roles in processing of genomic uracil . DNA Repair (Amsterdam)11 ( 6 ), 587 – 593 ( 2012 ).
  • Ulrich HD . Regulating post-translational modifications of the eukaryotic replication clamp PCNA . DNA Repair (Amsterdam)8 ( 4 ), 461 – 469 ( 2009 ).
  • Arakawa H , MoldovanGL , SaribasakH , SaribasakNN , JentschS , BuersteddeJM . A role for PCNA ubiquitination in immunoglobulin hypermutation . PLoS Biol.4 ( 11 ), e366 ( 2006 ).
  • Delbos F , AoufouchiS , FailiA , WeillJC , ReynaudCA . DNA polymerase eta is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse . J. Exp. Med.204 ( 1 ), 17 – 23 ( 2007 ).
  • Diaz M , VerkoczyLK , FlajnikMF , KlinmanNR . Decreased frequency of somatic hypermutation and impaired affinity maturation but intact germinal center formation in mice expressing antisense RNA to DNA polymerase zeta . J. Immunol.167 ( 1 ), 327 – 335 ( 2001 ).
  • Faili A , AoufouchiS , FlatterE , GuerangerQ , ReynaudCA , WeillJC . Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota . Nature419 ( 6910 ), 944 – 947 ( 2002 ).
  • Jansen JG , LangerakP , Tsaalbi-ShtylikA , Van Den BerkP , JacobsH , De WindN . Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice . J. Exp. Med.203 ( 2 ), 319 – 323 ( 2006 ).
  • Krijger PHL , LangerakP , Van Den BerkPCM , JacobsH . Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation . J. Exp. Med.206 ( 12 ), 2603 – 2611 ( 2009 ).
  • Langerak P , NygrenAO , KrijgerPH , Van Den BerkPC , JacobsH . A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification . J. Exp. Med.204 ( 8 ), 1989 – 1998 ( 2007 ).
  • Roa S , AvdievichE , PeledJUet al. Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression . Proc. Natl Acad. Sci. USA105 ( 42 ), 16248 – 16253 ( 2008 ).
  • Zan H , KomoriA , LiZet al. The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation . Immunity14 ( 5 ), 643 – 653 ( 2001 ).
  • Zeng X , WinterDB , KasmerC , KraemerKH , LehmannAR , GearhartPJ . DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes . Nat. Immunol.2 ( 6 ), 537 – 541 ( 2001 ).
  • Ranjit S , KhairL , LinehanEKet al. AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus . J. Immunol.187 ( 5 ), 2464 – 2475 ( 2011 ).
  • Vuong BQ , Herrick-ReynoldsK , VaidyanathanBet al. A DNA break- and phosphorylation-dependent positive feedback loop promotes immunoglobulin class-switch recombination . Nat. Immunol.14 ( 11 ), 1183 – 1189 ( 2013 ).
  • Navaratnam N , MorrisonJR , BhattacharyaSet al. The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase . J. Biol Chem.268 ( 28 ), 20709 – 20712 ( 1993 ).
  • Anant S , DavidsonNO . An AU-rich sequence element (UUUN[A/U]U) downstream of the edited C in apolipoprotein B mRNA is a high-affinity binding site for Apobec-1: binding of Apobec-1 to this motif in the 3’ untranslated region of c-myc increases mRNA stability . Mol. Cell Biol.20 ( 6 ), 1982 – 1992 ( 2000 ).
  • Anant S , MurmuN , HouchenCWet al. Apobec-1 protects intestine from radiation injury through posttranscriptional regulation of cyclooxygenase-2 expression . Gastroenterology127 ( 4 ), 1139 – 1149 ( 2004 ).
  • Xie Y , BlancV , KerrTAet al. Decreased expression of cholesterol 7alpha-hydroxylase and altered bile acid metabolism in Apobec-1-/- mice lead to increased gallstone susceptibility . J. Biol Chem.284 ( 25 ), 16860 – 16871 ( 2009 ).
  • Petersen-Mahrt SK , NeubergerMS . 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 ( 2003 ).
  • Bishop KN , HolmesRK , SheehyAM , MalimMH . APOBEC-mediated editing of viral RNA . Science305 ( 5684 ), 645 ( 2004 ).
  • Ikeda T , OhsugiT , KimuraTet al. The antiretroviral potency of APOBEC1 deaminase from small animal species . Nucleic Acids Res.36 ( 21 ), 6859 – 6871 ( 2008 ).
  • Petit V , GuetardD , RenardMet al. Murine APOBEC1 is a powerful mutator of retroviral and cellular RNA in vitro and in vivo . J. Mol. Biol.385 ( 1 ), 65 – 78 ( 2009 ).
  • Gee P , AndoY , KitayamaHet al. APOBEC1-mediated editing and attenuation of herpes simplex virus 1 DNA indicate that neurons have an antiviral role during herpes simplex encephalitis . J. Virol.85 ( 19 ), 9726 – 9736 ( 2011 ).
  • Sheehy AM , GaddisNC , ChoiJD , MalimMH . Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein . Nature418 ( 6898 ), 646 – 650 ( 2002 ).
  • Bogerd HP , CullenBR . Single-stranded RNA facilitates nucleocapsid: APOBEC3G complex formation . RNA14 ( 6 ), 1228 – 1236 ( 2008 ).
  • Khan MA , KaoS , MiyagiEet al. Viral RNA is required for the association of APOBEC3G with human immunodeficiency virus type 1 nucleoprotein complexes . J. Virol.79 ( 9 ), 5870 – 5874 ( 2005 ).
  • Schafer A , BogerdHP , CullenBR . Specific packaging of APOBEC3G into HIV-1 virions is mediated by the nucleocapsid domain of the gag polyprotein precursor . Virology328 ( 2 ), 163 – 168 ( 2004 ).
  • Svarovskaia ES , XuH , MbisaJLet al. Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is incorporated into HIV-1 virions through interactions with viral and nonviral RNAs . J. Biol Chem.279 ( 34 ), 35822 – 35828 ( 2004 ).
  • Yu Q , KonigR , PillaiSet al. Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome . Nat. Struct. Mol. Biol.11 ( 5 ), 435 – 442 ( 2004 ).
  • Harris RS , BishopKN , SheehyAMet al. DNA deamination mediates innate immunity to retroviral infection . Cell113 ( 6 ), 803 – 809 ( 2003 ).
  • Lecossier D , BouchonnetF , ClavelF , HanceAJ . Hypermutation of HIV-1 DNA in the absence of the Vif protein . Science300 ( 5622 ), 1112 ( 2003 ).
  • Mangeat B , TurelliP , CaronG , FriedliM , PerrinL , TronoD . Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts . Nature424 ( 6944 ), 99 – 103 ( 2003 ).
  • Zhang H , YangB , PomerantzRJ , ZhangC , ArunachalamSC , GaoL . The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA . Nature424 ( 6944 ), 94 – 98 ( 2003 ).
  • Weil AF , GhoshD , ZhouYet al. Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration . Proc. Natl Acad. Sci. USA110 ( 6 ), e448 – e457 ( 2013 ).
  • Conticello SG , HarrisRS , NeubergerMS . The Vif protein of HIV triggers degradation of the human antiretroviral DNA deaminase APOBEC3G . Curr. Biol.13 ( 22 ), 2009 – 2013 ( 2003 ).
  • Marin M , RoseKM , KozakSL , KabatD . HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation . Nat. Med.9 ( 11 ), 1398 – 1403 ( 2003 ).
  • Mehle A , StrackB , AncutaP , ZhangC , McpikeM , GabuzdaD . Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway . J. Biol Chem.279 ( 9 ), 7792 – 7798 ( 2004 ).
  • Sheehy AM , GaddisNC , MalimMH . The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif . Nat. Med.9 ( 11 ), 1404 – 1407 ( 2003 ).
  • Stopak K , De NoronhaC , YonemotoW , GreeneWC . HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability . Mol. Cell12 ( 3 ), 591 – 601 ( 2003 ).
  • Yu X , YuY , LiuBet al. Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex . Science302 ( 5647 ), 1056 – 1060 ( 2003 ).
  • Dang Y , WangX , EsselmanWJ , ZhengYH . Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family . J. Virol.80 ( 21 ), 10522 – 10533 ( 2006 ).
  • Delebecque F , SuspeneR , CalattiniSet al. Restriction of foamy viruses by APOBEC cytidine deaminases . J. Virol.80 ( 2 ), 605 – 614 ( 2006 ).
  • Zielonka J , BravoIG , MarinoDet al. Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases . J. Virol.83 ( 15 ), 7547 – 7559 ( 2009 ).
  • Hultquist JF , LengyelJA , RefslandEWet al. Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1 . J. Virol.85 ( 21 ), 11220 – 11234 ( 2011 ).
  • Harari A , OomsM , MulderLC , SimonV . Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H . J. Virol.83 ( 1 ), 295 – 303 ( 2009 ).
  • Ohainle M , KernsJA , LiMM , MalikHS , EmermanM . Antiretroelement activity of APOBEC3H was lost twice in recent human evolution . Cell Host Microbe4 ( 3 ), 249 – 259 ( 2008 ).
  • Tan L , SarkisPT , WangT , TianC , YuXF . Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1 . FASEB J.23 ( 1 ), 279 – 287 ( 2009 ).
  • Liddament MT , BrownWL , SchumacherAJ , HarrisRS . APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo . Curr. Biol.14 ( 15 ), 1385 – 1391 ( 2004 ).
  • Koning FA , NewmanEN , KimEY , KunstmanKJ , WolinskySM , MalimMH . Defining APOBEC3 expression patterns in human tissues and hematopoietic cell subsets . J. Virol.83 ( 18 ), 9474 – 9485 ( 2009 ).
  • Refsland EW , StengleinMD , ShindoK , AlbinJS , BrownWL , HarrisRS . Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction . Nucleic Acids Res.38 ( 13 ), 4274 – 4284 ( 2010 ).
  • Li Q , SmithAJ , SchackerTWet al. Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection . J. Immunol.183 ( 3 ), 1975 – 1982 ( 2009 ).
  • Simon V , ZennouV , MurrayD , HuangY , HoDD , BieniaszPD . Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification . PLoS Pathog.1 ( 1 ), e6 ( 2005 ).
  • Baumert TF , RoslerC , MalimMH , Von WeizsackerF . Hepatitis B virus DNA is subject to extensive editing by the human deaminase APOBEC3C . Hepatology46 ( 3 ), 682 – 689 ( 2007 ).
  • Bonvin M , AchermannF , GreeveIet al. Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication . Hepatology43 ( 6 ), 1364 – 1374 ( 2006 ).
  • Gunther S , SommerG , PlikatUet al. Naturally occurring hepatitis B virus genomes bearing the hallmarks of retroviral G‐‐>A hypermutation . Virology235 ( 1 ), 104 – 108 ( 1997 ).
  • Kock J , BlumHE . Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H . J. Gen. Virol.89 ( Pt 5 ), 1184 – 1191 ( 2008 ).
  • Noguchi C , HiragaN , MoriNet al. Dual effect of APOBEC3G on Hepatitis B virus . J. Gen. Virol.88 ( Pt 2 ), 432 – 440 ( 2007 ).
  • Noguchi C , ImamuraM , TsugeMet al. G-to-A hypermutation in hepatitis B virus (HBV) and clinical course of patients with chronic HBV infection . J. Infect. Dis199 ( 11 ), 1599 – 1607 ( 2009 ).
  • Noguchi C , IshinoH , TsugeMet al. G to A hypermutation of hepatitis B virus . Hepatology41 ( 3 ), 626 – 633 ( 2005 ).
  • Rosler C , KockJ , MalimMH , BlumHE , Von WeizsackerF . Comment on “Inhibition of hepatitis B virus replication by APOBEC3G” . Science305 ( 5689 ), 1403; author reply 1403 ( 2004 ).
  • Suspene R , GuetardD , HenryM , SommerP , Wain-HobsonS , VartanianJP . Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo . Proc. Natl Acad. Sci. USA102 ( 23 ), 8321 – 8326 ( 2005 ).
  • Turelli P , MangeatB , JostS , VianinS , TronoD . Inhibition of hepatitis B virus replication by APOBEC3G . Science303 ( 5665 ), 1829 ( 2004 ).
  • Vartanian JP , HenryM , MarchioAet al. Massive APOBEC3 editing of hepatitis B viral DNA in cirrhosis . PLoS Pathog.6 ( 5 ), e1000928 ( 2010 ).
  • Chen H , LilleyCE , YuQet al. APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons . Curr. Biol.16 ( 5 ), 480 – 485 ( 2006 ).
  • Narvaiza I , LinfestyDC , GreenerBNet al. Deaminase-independent inhibition of parvoviruses by the APOBEC3A cytidine deaminase . PLoS Pathog.5 ( 5 ), e1000439 ( 2009 ).
  • Vartanian JP , GuetardD , HenryM , Wain-HobsonS . Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions . Science320 ( 5873 ), 230 – 233 ( 2008 ).
  • Wang Z , WakaeK , KitamuraKet al. APOBEC3 deaminases induce hypermutation in human papillomavirus 16 DNA upon beta interferon stimulation . J. Virol.88 ( 2 ), 1308 – 1317 ( 2014 ).
  • Tsuge M , NoguchiC , AkiyamaRet al. G to A hypermutation of TT virus . Virus Res.149 ( 2 ), 211 – 216 ( 2010 ).
  • Huang CR , BurnsKH , BoekeJD . Active transposition in genomes . Annu. Rev. Genet.46 , 651 – 675 ( 2012 ).
  • Koito A , IkedaT . Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases . Front. Microbiol.4 , 28 ( 2013 ).
  • Esnault C , HeidmannO , DelebecqueFet al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses . Nature433 ( 7024 ), 430 – 433 ( 2005 ).
  • Esnault C , MilletJ , SchwartzO , HeidmannT . Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses . Nucleic Acids Res.34 ( 5 ), 1522 – 1531 ( 2006 ).
  • Schumacher AJ , NissleyDV , HarrisRS . APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast . Proc. Natl Acad. Sci. USA102 ( 28 ), 9854 – 9859 ( 2005 ).
  • Bogerd HP , WiegandHL , DoehleBP , LuedersKK , CullenBR . APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells . Nucleic Acids Res.34 ( 1 ), 89 – 95 ( 2006 ).
  • Bogerd HP , WiegandHL , HulmeAEet al. Cellular inhibitors of long interspersed element 1 and Alu retrotransposition . Proc. Natl Acad. Sci. USA103 ( 23 ), 8780 – 8785 ( 2006 ).
  • Hulme AE , BogerdHP , CullenBR , MoranJV . Selective inhibition of Alu retrotransposition by APOBEC3G . Gene390 ( 1–2 ), 199 – 205 ( 2007 ).
  • Muckenfuss H , HamdorfM , HeldUet al. APOBEC3 proteins inhibit human LINE-1 retrotransposition . J. Biol Chem.281 ( 31 ), 22161 – 22172 ( 2006 ).
  • Stenglein MD , HarrisRS . APOBEC3B and APOBEC3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism . J. Biol Chem.281 ( 25 ), 16837 – 16841 ( 2006 ).
  • Chiu YL , WitkowskaHE , HallSCet al. High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition . Proc. Natl Acad. Sci. USA103 ( 42 ), 15588 – 15593 ( 2006 ).
  • Hiom K , MelekM , GellertM . DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations . Cell94 ( 4 ), 463 – 470 ( 1998 ).
  • Gourzi P , LeonovaT , PapavasiliouFN . A role for activation-induced cytidine deaminase in the host response against a transforming retrovirus . Immunity24 ( 6 ), 779 – 786 ( 2006 ).
  • Macduff DA , DemorestZL , HarrisRS . AID can restrict L1 retrotransposition suggesting a dual role in innate and adaptive immunity . Nucleic Acids Res.37 ( 6 ), 1854 – 1867 ( 2009 ).
  • Metzner M , JackHM , WablM . LINE-1 retroelements complexed and inhibited by activation induced cytidine deaminase . PLoS One7 ( 11 ), e49358 ( 2012 ).
  • Bird A . DNA methylation patterns and epigenetic memory . Genes Dev.16 ( 1 ), 6 – 21 ( 2002 ).
  • Reik W , DeanW , WalterJ . Epigenetic reprogramming in mammalian development . Science293 ( 5532 ), 1089 – 1093 ( 2001 ).
  • Law JA , JacobsenSE . Establishing, maintaining and modifying DNA methylation patterns in plants and animals . Nat. Rev. Genet.11 ( 3 ), 204 – 220 ( 2010 ).
  • Mayer W , NiveleauA , WalterJ , FundeleR , HaafT . Demethylation of the zygotic paternal genome . Nature403 ( 6769 ), 501 – 502 ( 2000 ).
  • Oswald J , EngemannS , LaneNet al. Active demethylation of the paternal genome in the mouse zygote . Curr. Biol.10 ( 8 ), 475 – 478 ( 2000 ).
  • Santos F , HendrichB , ReikW , DeanW . Dynamic reprogramming of DNA methylation in the early mouse embryo . Dev. Biol.241 ( 1 ), 172 – 182 ( 2002 ).
  • Hajkova P , ErhardtS , LaneNet al. Epigenetic reprogramming in mouse primordial germ cells . Mech. Dev.117 ( 1–2 ), 15 – 23 ( 2002 ).
  • Lee J , InoueK , OnoRet al. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells . Development129 ( 8 ), 1807 – 1817 ( 2002 ).
  • Wu SC , ZhangY . Active DNA demethylation: many roads lead to Rome . Nat. Rev. Mol. Cell Biol.11 ( 9 ), 607 – 620 ( 2010 ).
  • Pauklin S , SernandezIV , BachmannG , RamiroAR , Petersen-MahrtSK . Estrogen directly activates AID transcription and function . J. Exp. Med.206 ( 1 ), 99 – 111 ( 2009 ).
  • Rai K , HugginsIJ , JamesSR , KarpfAR , JonesDA , CairnsBR . DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45 . Cell135 ( 7 ), 1201 – 1212 ( 2008 ).
  • Hendrich B , HardelandU , NgHH , JiricnyJ , BirdA . The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites . Nature401 ( 6750 ), 301 – 304 ( 1999 ).
  • Barreto G , SchaferA , MarholdJet al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation . Nature445 ( 7128 ), 671 – 675 ( 2007 ).
  • Schmitz KM , SchmittN , Hoffmann-RohrerU , SchaferA , GrummtI , MayerC . TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation . Mol. Cell33 ( 3 ), 344 – 353 ( 2009 ).
  • Liao W , HongSH , ChanBH , RudolphFB , ClarkSC , ChanL . APOBEC-2, a cardiac- and skeletal muscle-specific member of the cytidine deaminase supergene family . Biochem. Biophys. Res. Commun.260 ( 2 ), 398 – 404 ( 1999 ).
  • Mikl MC , WattIN , LuMet al. Mice deficient in APOBEC2 and APOBEC3 . Mol. Cell Biol.25 ( 16 ), 7270 – 7277 ( 2005 ).
  • Sato Y , ProbstHC , TatsumiR , IkeuchiY , NeubergerMS , RadaC . Deficiency in APOBEC2 leads to a shift in muscle fiber type, diminished body mass, and myopathy . J. Biol Chem.285 ( 10 ), 7111 – 7118 ( 2010 ).
  • Abdouni H , KingJJ , SulimanM , QuinlanM , FifieldH , LarijaniM . Zebrafish AID is capable of deaminating methylated deoxycytidines . Nucleic Acids Res.41 ( 10 ), 5457 – 5468 ( 2013 ).
  • Powell C , ElsaeidiF , GoldmanD . Injury-dependent Muller glia and ganglion cell reprogramming during tissue regeneration requires Apobec2a and Apobec2b . J. Neurosci.32 ( 3 ), 1096 – 1109 ( 2012 ).
  • Vonica A , RosaA , ArduiniBL , BrivanlouAH . APOBEC2, a selective inhibitor of TGFbeta signaling, regulates left-right axis specification during early embryogenesis . Dev. Biol.350 ( 1 ), 13 – 23 ( 2011 ).
  • Bhutani N , BradyJJ , DamianM , SaccoA , CorbelSY , BlauHM . Reprogramming towards pluripotency requires AID-dependent DNA demethylation . Nature463 ( 7284 ), 1042 – 1047 ( 2010 ).
  • Bhutani N , DeckerMN , BradyJJet al. A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells . FASEB J.27 ( 3 ), 1107 – 1113 ( 2013 ).
  • Kumar R , DimennaL , SchrodeNet al. AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes . Nature500 ( 7460 ), 89 – 92 ( 2013 ).
  • Rai K , SarkarS , BroadbentTJet al. DNA demethylase activity maintains intestinal cells in an undifferentiated state following loss of APC . Cell142 ( 6 ), 930 – 942 ( 2010 ).
  • Popp C , DeanW , FengSet al. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency . Nature463 ( 7284 ), 1101 – 1105 ( 2010 ).
  • Santos F , PeatJ , BurgessH , RadaC , ReikW , DeanW . Active demethylation in mouse zygotes involves cytosine deamination and base excision repair . Epigenetics Chromatin6 ( 1 ), 39 ( 2013 ).
  • Carpenter MA , LiM , RathoreAet al. Methylcytosine and normal cytosine deamination by the foreign DNA restriction enzyme APOBEC3A . J. Biol Chem.287 ( 41 ), 34801 – 34808 ( 2012 ).
  • Wijesinghe P , BhagwatAS . Efficient deamination of 5-methylcytosines in DNA by human APOBEC3A, but not by AID or APOBEC3G . Nucleic Acids Res.40 ( 18 ), 9206 – 9217 ( 2012 ).
  • Marchetto MCN , NarvaizaI , DenliAMet al. Differential L1 regulation in pluripotent stem cells of humans and apes . Nature503 ( 7477 ), 525 – 529 ( 2013 ).
  • Pastor WA , AravindL , RaoA . TETonic shift: biological roles of TET proteins in DNA demethylation and transcription . Nat. Rev. Mol. Cell Biol.14 ( 6 ), 341 – 356 ( 2013 ).
  • Tahiliani M , KohKP , ShenYet al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 . Science324 ( 5929 ), 930 – 935 ( 2009 ).
  • Guo JU , SuY , ZhongC , MingGL , SongH . Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain . Cell145 ( 3 ), 423 – 434 ( 2011 ).
  • Cortellino S , XuJ , SannaiMet al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair . Cell146 ( 1 ), 67 – 79 ( 2011 ).
  • Nabel CS , JiaH , YeYet al. AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation . Nat. Chem. Biol.8 ( 9 ), 751 – 758 ( 2012 ).
  • Rangam G , SchmitzKM , CobbAJ , Petersen-MahrtSK . AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud . PLoS One7 ( 8 ), e43279 ( 2012 ).
  • Millar CB , GuyJ , SansomOJet al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice . Science297 ( 5580 ), 403 – 405 ( 2002 ).
  • Santos F , DeanW . Epigenetic reprogramming during early development in mammals . Reproduction127 ( 6 ), 643 – 651 ( 2004 ).
  • Cortazar D , KunzC , SelfridgeJet al. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability . Nature470 ( 7334 ), 419 – 423 ( 2011 ).
  • Maiti A , DrohatAC . Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites . J. Biol Chem.286 ( 41 ), 35334 – 35338 ( 2011 ).
  • Hu XV , RodriguesTM , TaoHet al. Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen . Proc. Natl Acad. Sci. USA107 ( 34 ), 15087 – 15092 ( 2010 ).
  • Hardeland U , SteinacherR , JiricnyJ , SchärP . Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover . EMBO J.21 ( 6 ), 1456 – 1464 ( 2002 ).
  • May A , KirchnerR , MullerHet al. Multiplex rt-PCR expression analysis of developmentally important genes in individual mouse preimplantation embryos and blastomeres . Biol. Reprod.80 ( 1 ), 194 – 202 ( 2009 ).
  • Ruddock-D’cruz NT , XueJ , WilsonKJet al. Dynamic changes in the localization of five members of the methyl binding domain (MBD) gene family during murine and bovine preimplantation embryo development . Mol. Reprod. Dev.75 ( 1 ), 48 – 59 ( 2008 ).
  • Hajkova P , JeffriesSJ , LeeC , MillerN , JacksonSP , SuraniMA . Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway . Science329 ( 5987 ), 78 – 82 ( 2010 ).
  • Deans B , GriffinCS , MaconochieM , ThackerJ . Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice . EMBO J.19 ( 24 ), 6675 – 6685 ( 2000 ).
  • Gu H , MarthJD , OrbanPC , MossmannH , RajewskyK . Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting . Science265 ( 5168 ), 103 – 106 ( 1994 ).
  • Tebbs RS , FlanneryML , MenesesJJet al. Requirement for the Xrcc1 DNA base excision repair gene during early mouse development . Dev. Biol.208 ( 2 ), 513 – 529 ( 1999 ).
  • Pena-Diaz J , JiricnyJ . Mammalian mismatch repair: error-free or error-prone?Trends Biochem. Sci.37 ( 5 ), 206 – 214 ( 2012 ).
  • Jaroudi S , KakourouG , CawoodSet al. Expression profiling of DNA repair genes in human oocytes and blastocysts using microarrays . Hum. Reprod.24 ( 10 ), 2649 – 2655 ( 2009 ).
  • Menezo Y Jr , RussoG , TostiE , El MouatassimS , BenkhalifaM . Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays . J. Assist. Reprod. Genet.24 ( 11 ), 513 – 520 ( 2007 ).
  • Liu M , DukeJL , RichterDJet al. Two levels of protection for the B cell genome during somatic hypermutation . Nature451 ( 7180 ), 841 – 845 ( 2008 ).
  • Honjo T , KobayashiM , BegumN , KotaniA , SabouriS , NagaokaH . The AID dilemma: infection, or cancer?Adv. Cancer Res.113 , 1 – 44 ( 2012 ).
  • Incorvaia E , SicouriL , Petersen-MahrtSK , SchmitzKM . Hormones and AID. balancing immunity and autoimmunity . Autoimmunity46 ( 2 ), 128 – 137 ( 2013 ).
  • Beale RC , Petersen-MahrtSK , WattIN , HarrisRS , RadaC , NeubergerMS . Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo . J. Mol. Biol.337 ( 3 ), 585 – 596 ( 2004 ).

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