AIDing antibody diversity by error-prone mismatch repair

Seminars in Immunology

Volumn 24, Issue 4, 2012, Pages 293-300

  Chahwan, Richard ^a   Edelmann, Winfried ^a   Scharff, Matthew D ^a   Roa, Sergio ^b  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF NAVARRA   (Spain)

Author keywords

Activation induced deaminase; Antibody diversity; Class switch recombination; Cytosine deamination; Double strand breaks; Epigenetic; Mismatch repair; Somatic hypermutation

Indexed keywords

5 HYDROXYMETHYLCYTOSINE; ACTIVATION INDUCED CYTIDINE DEAMINASE; CYCLINE; ENDONUCLEASE; IMMUNOGLOBULIN;

ANTIBODY SPECIFICITY; B LYMPHOCYTE; DEMETHYLATION; DNA REPLICATION; DNA STRAND; ENZYME ACTIVITY; EPIGENETICS; GENOME; IN VIVO STUDY; MISMATCH REPAIR; MUTAGENESIS; NONHUMAN; PROTEIN EXPRESSION; REPORTER GENE; REVIEW; SOMATIC HYPERMUTATION; UBIQUITINATION;

ANIMALS; ANTIBODY DIVERSITY; CYTIDINE DEAMINASE; DEAMINATION; DNA MISMATCH REPAIR; HUMANS; MUTATION; UBIQUITINATION;

EID: 84865166222     PISSN: 10445323     EISSN: 10963618     Source Type: Journal    
DOI: 10.1016/j.smim.2012.05.005     Document Type: Review

References (121)

1. Jackson S.P., Bartek J. The DNA-damage response in human biology and disease. Nature 2009, 461:1071-1078.
2. Ingenuity systems, . http://www.ingenuity.com/.
3. Marcon E., Moens P.B. The evolution of meiosis: recruitment and modification of somatic DNA-repair proteins. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology 2005, 27:795-808.
4. Maul R.W., Gearhart P.J. AID and somatic hypermutation. Advances in Immunology 2010, 105:159-191.
5. Kracker S., Gardes P., Durandy A. Inherited defects of immunoglobulin class switch recombination. Advances in Experimental Medicine and Biology 2010, 685:166-174.
6. Lieber M.R. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annual Review of Biochemistry 2010, 79:181-211.
7. Teng G., Papavasiliou F.N. Immunoglobulin somatic hypermutation. Annual Review of Genetics 2007, 41:107-120.
8. Peled J.U., Kuang F.L., Iglesias-Ussel M.D., Roa S., Kalis S.L., Goodman M.F., et al. The biochemistry of somatic hypermutation. Annual Review of Immunology 2008, 26:481-511.
9. Stavnezer J., Guikema J.E.J., Schrader C.E. Mechanism and regulation of class switch recombination. Annual Review of Immunology 2008, 26:261-292.
10. Kracker S., Durandy A. Insights into the B cell specific process of immunoglobulin class switch recombination. Immunology Letters 2011, 138:97-103.
11. Han S., Zheng B., Takahashi Y., Kelsoe G. Distinctive characteristics of germinal center B cells. Seminars in Immunology 1997, 9:255-260.
12. Iyer R.R., Pluciennik A., Burdett V., Modrich P.L. DNA mismatch repair: functions and mechanisms. Chemical Reviews 2006, 106:302-323.
13. 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. Molecular Cell 2004, 16:163-171.
14. Green B., Belcheva A., Nepal R.M., Boulianne B., Martin A. The mismatch repair pathway functions normally at a non-AID target in germinal center B cells. Blood 2011, 118:3013-3018.
15. Liu M., Duke J.L., Richter D.J., Vinuesa C.G., Goodnow C.C., Kleinstein S.H., et al. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451:841-845.
16. Yamane A., Resch W., Kuo N., Kuchen S., Li Z., Sun H.W., et al. Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nature Immunology 2011, 12:62-69.
17. Popp C., Dean W., Feng S., Cokus S.J., Andrews S., Pellegrini M., et al. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 2010, 463:1101-1105.
18. 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. The Journal of Biological Chemistry 2004, 279:52353-52360.
19. Bhutani N., Brady J.J., Damian M., Sacco A., Corbel S.Y., Blau H.M. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 2009, 463:1042-1047.
20. Guo J.U., Su Y., Zhong C., Ming G.L., Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 2011, 145:423-434.
21. Pavri R., Gazumyan A., Jankovic M., Di Virgilio M., Klein I., Ansarah-Sobrinho C., et al. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. Cell 2010, 143:122-133.
22. Ronai D., Iglesias-Ussel M.D., Fan M., Li Z., Martin A., Scharff M.D. Detection of chromatin-associated single-stranded DNA in regions targeted for somatic hypermutation. The Journal of Experimental Medicine 2007, 204:181-190.
23. Larijani M., Martin A. Single-stranded DNA structure and positional context of the target cytidine determine the enzymatic efficiency of AID. Molecular and Cellular Biology 2007, 27:8038-8048.
24. 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. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:4102-4107.
25. Tanaka A., Shen H.M., Ratnam S., Kodgire P., Storb U. Attracting AID to targets of somatic hypermutation. The Journal of Experimental Medicine 2010, 207:405-415.
26. Michael N., Shen H.M., Longerich S., Kim N., Longacre A., The Storb U. E box motif CAGGTG enhances somatic hypermutation without enhancing transcription. Immunity 2003, 19:235-242.
27. Kuang F., Luo Z., Scharff M.D. H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination. Proceedings of the National Academy of Sciences of the United States of America 2009, 106:5288-5293.
28. Wang L., Whang N., Wuerffel R., Kenter A.L. AID-dependent histone acetylation is detected in immunoglobulin S regions. The Journal of Experimental Medicine 2006, 203:215-226.
29. Woo C.J., Martin A., Scharff M.D. Induction of hypermutation is associated with modifications of variable region chromatin in BL2 cells. Immunity 2003, 19:479-489.
30. Odegard V.H., Kim S.T., Anderson S.M., Shlomchik M.J., Schatz D.G. Histone modifications associated with somatic hypermutation. Immunity 2005, 23:101-110.
31. Chahwan R., Wontakal S.N., Roa S. Crosstalk between genetic and epigenetic information through cytosine deamination. Trends in Genetics 2010, 26:443-448.
32. Rai K., Huggins I.J., James S.R., Karpf A.R., Jones D.A., Cairns B.R. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 2008, 135:1201-1212.
33. Cortellino S., Xu J., Sannai M., Moore R., Caretti E., Cigliano A., et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 2011, 146:67-79.
34. Okazaki I.M., Kotani A., Honjo T. Role of AID in tumorigenesis. Advances in Immunology 2007, 94:245-273.
35. Marusawa H., Takai A., Chiba T. Role of activation-induced cytidine deaminase in inflammation-associated cancer development. Advances in Immunology 2011, 111:109-141.
36. Martin A., Li Z., Lin D., Bardwell P.D., Iglesias-Ussel M.D., Edelmann W., et al. Msh2 ATPase activity is essential for somatic hypermutation at A-T basepairs and for efficient class switch recombination. Journal of Experimental Medicine 2003, 198:1171-1178.
37. Li Z., Zhao C., Iglesias-Ussel M.D., Polonskaya Z., Zhuang M., Yang G., et al. The mismatch repair protein Msh6 influences the in vivo AID targeting to the Ig locus. Immunity 2006, 24:393-403.
38. Jiricny J. The multifaceted mismatch-repair system. Nature Reviews Molecular Cell Biology 2006, 7:335-346.
39. Bardwell P.D., Woo C.J., Wei K., Li Z., Martin A., Sack S.Z., et al. Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice. Nature Immunology 2004, 5:224-229.
40. Matsuda T., Bebenek K., Masutani C., Rogozin I.B., Hanaoka F., Kunkel T.A. Error rate and specificity of human and murine DNA polymerase eta. Journal of Molecular Biology 2001, 312:335-346.
41. Zeng X., Winter D.B., Kasmer C., Kraemer K.H., Lehmann A.R., Gearhart P.J. DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nature Immunology 2001, 2:537-541.
42. Martomo S.A., Yang W.W., Wersto R.P., Ohkumo T., Kondo Y., Yokoi M., et al. Different mutation signatures in DNA polymerase eta- and MSH6-deficient mice suggest separate roles in antibody diversification. Proceedings of the National Academy of Sciences of the United States of America 2005, 102:8656-8661.
43. Delbos F., Aoufouchi S., Faili A., Weill J.C., Reynaud C.A. DNA polymerase eta is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse. The Journal of Experimental Medicine 2007, 204:17-23.
44. Faili A., Stary A., Delbos F., Weller S., Aoufouchi S., Sarasin A., et al. A backup role of DNA polymerase kappa in Ig gene hypermutation only takes place in the complete absence of DNA polymerase eta. Journal of Immunology 2009, 182:6353-6359.
45. Langerak P., Nygren A.O., Krijger P.H., van den Berk P.C., Jacobs H. A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification. The Journal of Experimental Medicine 2007, 204:1989-1998.
46. Roa S., Avdievich E., Peled J.U., Maccarthy T., Werling U., Kuang F.L., et al. Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:16248-16253.
47. Larijani M., Petrov A.P., Kolenchenko O., Berru M., Krylov S.N., Martin A. AID associates with single-stranded DNA with high affinity and a long complex half-life in a sequence-independent manner. Molecular and Cellular Biology 2007, 27:20-30.
48. Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E., et al. Reconstitution of 5'-directed human mismatch repair in a purified system. Cell 2005, 122:693-705.
49. Genschel J., Modrich P. Functions of MutLalpha, replication protein A (RPA), and HMGB1 in 5'-directed mismatch repair. The Journal of Biological Chemistry 2009, 284:21536-21544.
50. Kadyrov F.A., Dzantiev L., Constantin N., Modrich P. Endonucleolytic function of MutLalpha in human mismatch repair. Cell 2006, 126:297-308.
51. Kadyrov F.A., Holmes S.F., Arana M.E., Lukianova O.A., O'Donnell M., Kunkel T.A., et al. Saccharomyces cerevisiae MutL{alpha} Is a Mismatch Repair Endonuclease. The Journal of Biological Chemistry 2007, 282:37181-37190.
52. van Oers J.M., Roa S., Werling U., Liu Y., Genschel J., Hou H., et al. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. Proceedings of the National Academy of Sciences of the United States of America 2010, 107:13384-13389.
53. Chahwan R., Edelmann W., Scharff M.D., Roa S. Mismatch-mediated error prone repair at the immunoglobulin genes. Biomedicine & Pharmacotherapy=Biomedecine & Pharmacotherapie 2011, 65:529-536.
54. Modrich P. Mechanisms in eukaryotic mismatch repair. The Journal of Biological Chemistry 2006, 281:30305-30309.
55. 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. Current Biology 2002, 12:1748-1755.
56. Rada C., Ehrenstein M.R., Neuberger M.S., Milstein C. Hot spot focusing of somatic hypermutation in MSH2-deficient mice suggests two stages of mutational targeting. Immunity 1998, 9:135-141.
57. Di Noia J., Neuberger M.S. Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002, 419:43-48.
58. Wiesendanger M., Kneitz B., Edelmann W., Scharff M.D. Somatic mutation in MSH3, MSH6, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern. Journal of Experimental Medicine 2000, 191:579-584.
59. Shen H.M., Tanaka A., Bozek G., Nicolae D., Storb U. Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice. Journal of Immunology 2006, 177:5386-5392.
60. Krijger P.H., Langerak P., van den Berk P.C., Jacobs H. Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation. The Journal of Experimental Medicine 2009, 206:2603-26011.
61. Frieder D., Larijani M., Collins C., Shulman M., Martin A. The concerted action of Msh2 and UNG stimulates somatic hypermutation at A·T base pairs. Molecular and Cellular Biology 2009, 29:5148-5157.
62. Roa S., Li Z., Peled J.U., Zhao C., Edelmann W., Scharff M.D. MSH2/MSH6 complex promotes error-free repair of AID-induced dU:G mispairs as well as error-prone hypermutation of A:T sites. PLoS One 2010, 5:e11182.
63. Arakawa H., Moldovan G.L., Saribasak H., Saribasak N.N., Jentsch S., Buerstedde J.M. A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS Biology 2006, 4:e366.
64. Hoege C., Pfander B., Moldovan G.L., Pyrowolakis G., Jentsch S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 2002, 419:135-141.
65. Kannouche P.L., Wing J., Lehmann A.R. Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Molecular Cell 2004, 14:491-500.
66. Krijger P.H., Lee K.Y., Wit N., van den Berk P.C., Wu X., Roest H.P., et al. HLTF and SHPRH are not essential for PCNA polyubiquitination, survival and somatic hypermutation: Existence of an alternative E3 ligase. DNA Repair (Amsterdam) 2011, 10:438-444.
67. Motegi A., Liaw H.J., Lee K.Y., Roest H.P., Maas A., Wu X., et al. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:12411-12416.
68. Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K. Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. Journal of Cell Biology 2006, 175:703-708.
69. Ukai A., Ishimaru K., Ouchida R., Mori H., Kano C., Moritan T., et al. Induction of a:T mutations is dependent on cellular environment but independent of mutation frequency and target gene location. Journal of Immunology 2008, 181:7835-7842.
70. Ouchida R., Ukai A., Mori H., Kawamura K., Dolle M.E., Tagawa M., et al. Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A:T mutations. DNA Repair (Amsterdam) 2008, 7:1392-1398.
71. Rush J.S., Fugmann S.D., Schatz D.G. Staggered AID-dependent DNA double strand breaks are the predominant DNA lesions targeted to S mu in Ig class switch recombination. International Immunology 2004, 16:549-557.
72. Stavnezer J., Schrader C.E. Mismatch repair converts AID-instigated nicks to double-strand breaks for antibody class-switch recombination. Trends in Genetics 2006, 22:23-28.
73. Stavnezer J., Bjorkman A., Du L., Cagigi A., Pan-Hammarstrom Q. Mapping of switch recombination junctions, a tool for studying DNA repair pathways during immunoglobulin class switching. Advances in Immunology 2010, 108:45-109.
74. Ise W., Kohyama M., Schraml B.U., Zhang T., Schwer B., Basu U., et al. The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nature Immunology 2011, 12:536-543.
75. Sellars M., Reina-San-Martin B., Kastner P., Chan S. Ikaros controls isotype selection during immunoglobulin class switch recombination. The Journal of Experimental Medicine 2009, 206:1073-1087.
76. Pinaud E., Khamlichi A.A., Le Morvan C., Drouet M., Nalesso V., Le Bert M., et al. Localization of the 3' IgH locus elements that effect long-distance regulation of class switch recombination. Immunity 2001, 15:187-199.
77. Manis J.P., van der Stoep N., Tian M., Ferrini R., Davidson L., Bottaro A., et al. Class switching in B cells lacking 3' immunoglobulin heavy chain enhancers. The Journal of Experimental Medicine 1998, 188:1421-1431.
78. Ju Z., Chatterjee S., Birshtein B.K. Interaction between the immunoglobulin heavy chain 3' regulatory region and the IgH transcription unit during B cell differentiation. Molecular Immunology 2011, 49:297-303.
79. Wuerffel R., Wang L., Grigera F., Manis J., Selsing E., Perlot T., et al. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase. Immunity 2007, 27:711-722.
80. Zarrin A.A., Alt F.W., Chaudhuri J., Stokes N., Kaushal D., Du Pasquier L., et al. An evolutionarily conserved target motif for immunoglobulin class-switch recombination. Nature Immunology 2004, 5:1275-1281.
81. Yu K., Roy D., Bayramyan M., Haworth I.S., Lieber M.R. Fine-structure analysis of activation-induced deaminase accessibility to class switch region R-loops. Molecular and Cellular Biology 2005, 25:1730-1736.
82. 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 Research 2003, 31:2990-2994.
83. Huang F.T., Yu K., Balter B.B., Selsing E., Oruc Z., Khamlichi A.A., et al. Sequence dependence of chromosomal R-loops at the immunoglobulin heavy-chain Smu class switch region. Molecular and Cellular Biology 2007, 27:5921-5932.
84. Michael N., Martin T.E., Nicolae D., Kim N., Padjen K., Zhan P., et al. Effects of sequence and structure on the hypermutability of immunoglobulin genes. Immunity 2002, 16:123-134.
85. Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J., et al. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 2011, 144:353-363.
86. Shen H.M., Storb U. Activation-induced cytidine deaminase (AID) can target both DNA strands when the DNA is supercoiled. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:12997-13002.
87. Shen H.M., Ratnam S., Storb U. Targeting of the activation-induced cytosine deaminase is strongly influenced by the sequence and structure of the targeted DNA. Molecular and Cellular Biology 2005, 25:10815-10821.
88. Schrader C.E., Bradley S.P., Vardo J., Mochegova S.N., Flanagan E., Stavnezer J. Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination. EMBO Journal 2003, 22:5893-5903.
89. Schrader C.E., Vardo J., Stavnezer J. Mlh1 can function in antibody class switch recombination independently of Msh2. The Journal of Experimental Medicine 2003, 197:1377-1383.
90. Kotnis A., Du L., Liu C., Popov S.W., Pan-Hammarstrom Q. Non-homologous end joining in class switch recombination: the beginning of the end. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 2009, 364:653-665.
91. Peron S., Metin A., Gardes P., Alyanakian M.A., Sheridan E., Kratz C.P., et al. Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. The Journal of Experimental Medicine 2008, 205:2465-2472.
92. Gardes P., Forveille M., Alyanakian M.A., Aucouturier P., Ilencikova D., Leroux D., et al. Human MSH6 Deficiency Is Associated with Impaired Antibody Maturation. Journal of Immunology 2012, 188:2023-2029.
93. Dinkelmann M., Spehalski E., Stoneham T., Buis J., Wu Y., Sekiguchi J.M., et al. Multiple functions of MRN in end-joining pathways during isotype class switching. Nature Structural & Molecular Biology 2009, 16:808-813.
94. Lee-Theilen M., Matthews A.J., Kelly D., Zheng S., Chaudhuri J. CtIP promotes microhomology-mediated alternative end joining during class-switch recombination. Nature Structural & Molecular Biology 2011, 18:75-79.
95. Schrader C.E., Vardo J., Stavnezer J. Role for mismatch repair proteins Msh2, Mlh1, and Pms2 in immunoglobulin class switching shown by sequence analysis of recombination junctions. The Journal of Experimental Medicine 2002, 195:367-373.
96. Schrader C.E., Edelmann W., Kucherlapati R., Stavnezer J. Reduced isotype switching in splenic B cells from mice deficient in mismatch repair enzymes. The Journal of Experimental Medicine 1999, 190:323-330.
97. Chahwan R., van Oers J.M., Avdievich E., Zhao C., Edelmann W., Scharff M.D., Roa S. The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination. The Journal of Experimental Medicine 2012, 209:671-678.
98. Cannavo E., Gerrits B., Marra G., Schlapbach R., Jiricny J. Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2. The Journal of Biological Chemistry 2007, 282:2976-2986.
99. Shahi A., Lee J.H., Kang Y., Lee S.H., Hyun J.W., Chang I.Y., et al. Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair. Nucleic Acids Research 2011, 39:2130-2143.
100. Zeng X., Negrete G.A., Kasmer C., Yang W.W., Gearhart P.J. Absence of DNA polymerase eta reveals targeting of C mutations on the nontranscribed strand in immunoglobulin switch regions. The Journal of Experimental Medicine 2004, 199:917-924.
101. Schöpf B., Bregenhorn S., Quivy J.P., Kadyrov F.A., Almouzni G., Jiricny J. Interplay between mismatch repair and chromatin assembly. Proceedings of the National Academy of Sciences of the United States of America 2012, 109:1895-1900.
102. Javaid S., Manohar M., Punja N., Mooney A., Ottesen J.J., Poirier M.G., et al. Nucleosome remodeling by hMSH2-hMSH6. Molecular Cell 2009, 36:1086-1094.
103. Li L.S., Morales J.C., Veigl M., Sedwick D., Greer S., Meyers M., et al. DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets. British Journal of Pharmacology 2009, 158:679-692.
104. Jeevan-Raj B.P., Robert I., Heyer V., Page A., Wang J.H., Cammas F., et al. Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. The Journal of Experimental Medicine 2011, 208:1649-1660.
105. Daniel J.A., Santos M.A., Wang Z., Zang C., Schwab K.R., Jankovic M., et al. PTIP promotes chromatin changes critical for immunoglobulin class switch recombination. Science (New York, NY) 2010, 329:917-923.
106. Mostoslavsky R., Alt F.W., Bassing C.H. Chromatin dynamics and locus accessibility in the immune system. Nature Immunology 2003, 4:603-606.
107. Gohler T., Munoz I.M., Rouse J., Blow J.J. PTIP/swift is required for efficient PCNA ubiquitination in response to DNA damage. DNA Repair (Amsterdam) 2008, 7:775-787.
108. Santos M.A., Huen M.S., Jankovic M., Chen H.T., Lopez-Contreras A.J., Klein I.A., et al. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. The Journal of Experimental Medicine 2010, 207:973-981.
109. Ramachandran S., Chahwan R., Nepal R.M., Frieder D., Panier S., Roa S., et al. The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proceedings of the National Academy of Sciences of the United States of America 2010, 107:809-814.
110. Zhang S., Chea J., Meng X., Zhou Y., Lee E.Y., Lee M.Y. PCNA is ubiquitinated by RNF8. Cell Cycle 2008, 7:3399-3404.
111. Sale J.E., Neuberger M.S. TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line. Immunity 1998, 9:859-869.
112. Zan H., Wu X., Komori A., Holloman W.K., Casali P. AID-dependent generation of resected double-strand DNA breaks and recruitment of Rad52/Rad51 in somatic hypermutation. Immunity 2003, 18:727-738.
113. Hasham M.G., Donghia N.M., Coffey E., Maynard J., Snow K.J., Ames J., et al. Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nature Immunology 2010, 11:820-826.
114. Ranjit S., Khair L., Linehan E.K., Ucher A.J., Chakrabarti M., Schrader C.E., et al. AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus. Journal of Immunology 2011, 187:2464-2475.
115. Xu Z., Fulop Z., Wu G., Pone E.J., Zhang J., Mai T., et al. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination. Nature Structural & Molecular Biology 2010, 17:1124-1135.
116. Meyers M., Hwang A., Wagner M.W., Bruening A.J., Veigl M.L., Sedwick W.D., et al. A role for DNA mismatch repair in sensing and responding to fluoropyrimidine damage. Oncogene 2003, 22:7376-7388.
117. Wang J.Y., Edelmann W. Mismatch repair proteins as sensors of alkylation DNA damage. Cancer Cell 2006, 9:417-418.
118. Stavnezer J. Complex regulation and function of activation-induced cytidine deaminase. Trends in Immunology 2011, 32:194-201.
119. Faili A., Aoufouchi S., Gueranger Q., Zober C., Leon A., Bertocci B., et al. AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nature Immunology 2002, 3:815-821.
120. 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. Journal of Immunology 2007, 179:6064-6071.
121. Hombauer H., Campbell C.S., Smith C.E., Desai A., Kolodner R.D. Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates. Cell 2011, 147:1040-1053.