DNA polymerases β and λ do not directly affect Ig variable region somatic hypermutation although their absence reduces the frequency of mutations

DNA Repair

Volumn 12, Issue 12, 2013, Pages 1087-1093

  Schrader, Carol E ^a   Linehan, Erin K ^a   Ucher, Anna J ^a   Bertocci, Barbara ^b   Stavnezer, Janet ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

A:T mutations; Activation induced cytidine deaminase; Base excision repair; Mismatch repair

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; DNA DIRECTED DNA POLYMERASE BETA; DNA DIRECTED DNA POLYMERASE GAMMA;

ANIMAL CELL; ARTICLE; B LYMPHOCYTE; BONE MARROW CELL; CONTROLLED STUDY; DNA FLANKING REGION; DNA RECOMBINATION; DNA REPLICATION; EMBRYO; FEMALE; FLOW CYTOMETRY; GENE LOCUS; GENOTYPE; GERMINAL CENTER; IMMUNOGLOBULIN VARIABLE REGION; LYMPHOCYTE PROLIFERATION; MISMATCH REPAIR; MOUSE; MUTATION RATE; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SINGLE STRANDED DNA BREAK; SOMATIC HYPERMUTATION; SPLEEN; T CELL DEPLETION; VDJ RECOMBINATION;

MUS;

A:T MUTATIONS; ACTIVATION INDUCED CYTIDINE DEAMINASE; AID; BASE EXCISION REPAIR; BER; CLASS SWITCH RECOMBINATION; CSR; DOUBLE-STRAND DNA BREAK; DSB; GC; GERMINAL CENTER; MISMATCH REPAIR; MMR; POL; POLYMERASE; SHM; SINGLE-STRAND DNA BREAK; SOMATIC HYPERMUTATION; SSB; UNG; URACIL-N-DNA GLYCOSYLASE;

ANIMALS; B-LYMPHOCYTES; CELLS, CULTURED; DNA BREAKS, DOUBLE-STRANDED; DNA POLYMERASE BETA; EMBRYO, MAMMALIAN; FEMALE; GENE DELETION; IMMUNOGLOBULIN CLASS SWITCHING; IMMUNOGLOBULIN G; IMMUNOGLOBULIN VARIABLE REGION; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUTATION RATE; POINT MUTATION; SOMATIC HYPERMUTATION, IMMUNOGLOBULIN;

EID: 84888135839     PISSN: 15687864     EISSN: 15687856     Source Type: Journal    
DOI: 10.1016/j.dnarep.2013.09.002     Document Type: Article

References (72)

1. 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.
2. Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., Catalan N., Forveille M., Dufourcq-Labelouse R., Gennery A., Tezcan I., Ersoy F., Kayserili H., Ugazio A.G., Brousse N., Muramatsu M., Notarangelo L.D., Kinoshita K., Honjo T., Fischer A., Durandy A. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000, 102:565-575.
3. Petersen-Mahrt S.K., Harris R.S., Neuberger M.S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 2002, 418:99-104.
4. 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., Gearhart P.J. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat. Immunol. 2011, 12:70-76.
5. Robbiani D.F., Nussenzweig M.C. Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase. Annu. Rev. Pathol. 2013, 8:79-103.
6. 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.
7. Staszewski O., Baker R.E., Ucher A.J., Martier R., Stavnezer J., Guikema J.E. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells. Mol. Cell 2011, 41:232-242.
8. Gostissa M., Alt F.W., Chiarle R. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annu. Rev. Immunol. 2011, 29:319-350.
9. Lindahl T. Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat. Res. 2000, 462:129-135.
10. 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.
11. Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R., Stavnezer J., Schrader C.E. APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. J. Exp. Med. 2007, 204:3017-3026.
12. Almeida K.H., Sobol R.W. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair (Amst.) 2007, 6:695-711.
13. Hadi M.Z., Ginalski K., Nguyen L.H., Wilson D.M. Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III. J. Mol. Biol. 2002, 316:853-866.
14. Braithwaite E.K., Prasad R., Shock D.D., Hou E.W., Beard W.A., Wilson S.H. DNA polymerase λ mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts. J. Biol. Chem. 2005, 280:18469-18475.
15. Braithwaite E.K., Kedar P.S., Stumpo D.J., Bertocci B., Freedman J.H., Samson L.D., Wilson S.H. DNA polymerases β and λ mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts. PLoS ONE 2010, 5:e12229.
16. Robertson A.B., Klungland A., Rognes T., Leiros I. DNA repair in mammalian cells: base excision repair: the long and short of it. Cell. Mol. Life Sci. 2009, 66:981-993.
17. Schrader C.E., Linehan E.K., Mochegova S.N., Woodland R.T., Stavnezer J. Inducible DNA breaks in Ig S regions are dependent upon AID and UNG. J. Exp. Med. 2005, 202:561-568.
18. Schrader C.E., Guikema J.E., Wu X., Stavnezer J. The roles of APE1, APE2, DNA polymerase β and mismatch repair in creating S region DNA breaks during antibody class switch. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009, 364:645-652.
19. Fung H., Demple B. A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells. Mol. Cell 2005, 17:463-470.
20. Wu X., Stavnezer J. DNA polymerase β is able to repair breaks in switch regions and plays an inhibitory role during immunoglobulin class switch recombination. J. Exp. Med. 2007, 204:1677-1689.
21. Huang F.T., Yu K., Balter B.B., Selsing E., Oruc Z., Khamlichi A.A., Hsieh C.L., Lieber M.R. Sequence-dependence of chromosomal R-loops at the immunoglobulin heavy chain Sμ class switch region. Mol. Cell. Biol. 2007, 27:5921-5932.
22. Stavnezer J. Complex regulation and function of activation-induced cytidine deaminase. Trends Immunol. 2011, 32:194-201.
23. Kenter A.L. AID targeting is dependent on RNA polymerase II pausing. Semin. Immunol. 2012, 24:281-286.
24. Esposito G., Texido G., Betz U.A., Gu H., Muller W., Klein U., Rajewsky K. Mice reconstituted with DNA polymerase β-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:1166-1171.
25. Poltoratsky V., Prasad R., Horton J.K., Wilson S.H. Down-regulation of DNA polymerase β accompanies somatic hypermutation in human BL2 cell lines. DNA Repair (Amst.) 2007, 6:244-253.
26. Bertocci B., De Smet A., Flatter E., Dahan A., Bories J.C., Landreau C., Weill J.C., Reynaud C.A. Cutting edge: DNA polymerases μ and λ are dispensable for Ig gene hypermutation. J. Immunol. 2002, 168:3702-3706.
27. Martomo S.A., Yang W.W., Wersto R.P., Ohkumo T., Kondo Y., Yokoi M., Masutani C., Hanaoka F., Gearhart P.J. Different mutation signatures in DNA polymerase η- and MSH6-deficient mice suggest separate roles in antibody diversification. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:8656-8661.
28. Delbos F., De Smet A., Faili A., Aoufouchi S., Weill J.C., Reynaud C.A. Contribution of DNA polymerase η to immunoglobulin gene hypermutation in the mouse. J. Exp. Med. 2005, 201:1191-1196.
29. Delbos F., Aoufouchi S., Faili A., Weill J.C., Reynaud C.A. DNA polymerase η is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse. J. Exp. Med. 2007, 204:17-23.
30. Gu H., Marth J.D., Orban P.C., Mossmann H., Rajewsky K. Deletion of a DNA polymerase β gene segment in T cells using cell type-specific gene targeting. Science 1994, 265:103-106.
31. McDonald J.P., Frank E.G., Plosky B.S., Rogozin I.B., Masutani C., Hanaoka F., Woodgate R., Gearhart P.J. 129-derived strains of mice are deficient in DNA polymerase ι and have normal immunoglobulin hypermutation. J. Exp. Med. 2003, 198:635-643.
32. 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.
33. Garcia-Diaz M., Bebenek K., Krahn J.M., Pedersen L.C., Kunkel T.A. Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase. Cell 2006, 124:331-342.
34. Bebenek K., Garcia-Diaz M., Blanco L., Kunkel T.A. The frameshift infidelity of human DNA polymerase λ. Implications for function. J. Biol. Chem. 2003, 278:34685-34690.
35. Bertocci B., De Smet A., Weill J.C., Reynaud C.A. Nonoverlapping functions of DNA polymerases μ, λ, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo. Immunity 2006, 25:31-41.
36. Christmann M., Tomicic M.T., Roos W.P., Kaina B. Mechanisms of human DNA repair: an update. Toxicology 2003, 193:3-34.
37. Ma Y., Lu H., Tippin B., Goodman M.F., Shimazaki N., Koiwai O., Hsieh C.L., Schwarz K., Lieber M.R. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol. Cell 2004, 16:701-713.
38. Lee J.W., Blanco L., Zhou T., Garcia-Diaz M., Bebenek K., Kunkel T.A., Wang Z., Povirk L.F. Implication of DNA polymerase λ in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts. J. Biol. Chem. 2004, 279:805-811.
39. Wilson T.M., Vaisman A., Martomo S.A., Sullivan P., Lan L., Hanaoka F., Yasui A., Woodgate R., Gearhart P.J. MSH2-MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes. J. Exp. Med. 2005, 201:637-645.
40. Arakawa H., Moldovan G.L., Saribasak H., Saribasak N.N., Jentsch S., Buerstedde J.M. A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS Biol. 2006, 4:e366.
41. Petersen S., Casellas R., Reina-San-Martin B., Chen H.T., Difilippantonio M.J., Wilson P.C., Hanitsch L., Celeste A., Muramatsu M., Pilch D.R., Redon C., Ried T., Bonner W.M., Honjo T., Nussenzweig M.C., Nussenzweig A. AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching. Nature 2001, 414:660-665.
42. 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.
43. Rooney S., Chaudhuri J., Alt F.W. The role of the non-homologous end-joining pathway in lymphocyte development. Immunol. Rev. 2004, 200:115-131.
44. Stavnezer J., Guikema J.E.J., Schrader C.E. Mechanism and regulation of class switch recombination. Ann. Rev. Immunol. 2008, 26:261-292.
45. 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.
46. Ranjit S., Khair L., Linehan E.K., Ucher A.J., Chakrabarti M., Schrader C.E., Stavnezer J. AID binds cooperatively with UNG and Msh2-Msh6 to Ig switch regions dependent upon the AID C terminus. J. Immunol. 2011, 187:2464-2475.
47. Ta V.T., Nagaoka H., Catalan N., Durandy A., Fischer A., Imai K., Nonoyama S., Tashiro J., Ikegawa M., Ito S., Kinoshita K., Muramatsu M., Honjo T. AID mutant analyses indicate requirement for class-switch-specific cofactors. Nat. Immunol. 2003, 4:843-848.
48. Barreto V., Reina-San-Martin B., Ramiro A.R., McBride K.M., Nussenzweig M.C. C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion. Mol. Cell 2003, 12:501-508.
49. Xu Z., Fulop Z., Wu G., Pone E.J., Zhang J., Mai T., Thomas L.M., Al-Qahtani A., White C.A., Park S.R., Steinacker P., Li Z., Yates J., Herron B., Otto M., Zan H., Fu H., Casali P. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination. Nat. Struct. Mol. Biol. 2010, 17:1124-1135.
50. Zan H., White C.A., Thomas L.M., Mai T., Li G., Xu Z., Zhang J., Casali P. Rev1 recruits Ung to switch regions and enhances dU glycosylation for immunoglobulin class switch DNA recombination. Cell reports 2012, 2:1220-1232.
51. Vuong B.Q., Lee M., Kabir S., Irimia C., Macchiarulo S., McKnight G.S., Chaudhuri J. Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination. Nat. Immunol. 2009, 10:420-426.
52. Nowak U., Matthews A.J., Zheng S., Chaudhuri J. The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA. Nat. Immunol. 2011, 12:160-166.
53. Jeevan-Raj B.P., Robert I., Heyer V., Page A., Wang J.H., Cammas F., Alt F.W., Losson R., Reina-San-Martin B. Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. J. Exp. Med. 2011, 208:1649-1660.
54. Zahn A., Daugan M., Safavi S., Godin D., Cheong C., Lamarre A., Di Noia J.M. Separation of function between isotype switching and affinity maturation in vivo during acute immune responses and circulating autoantibodies in UNG-deficient mice. J. Immunol. 2013, 190:5949-5960.
55. Storb U., Shen H.M., Nicolae D. Somatic hypermutation: processivity of the cytosine deaminase AID and error-free repair of the resulting uracils. Cell cycle 2009, 8:3097-3101.
56. Di Noia J., Neuberger M.S. Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002, 419:43-48.
57. Di Noia J.M., Rada C., Neuberger M.S. SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair. EMBO J. 2006, 25:585-595.
58. -/- double-knockout mice. J. Immunol. 2006, 177:5386-5392.
59. Perez-Duran P., Belver L., de Yebenes V.G., Delgado P., Pisano D.G., Ramiro A.R. UNG shapes the specificity of AID-induced somatic hypermutation. J. Exp. Med. 2012, 209:1379-1389.
60. -/- mice suggests that UNG and A:T mutagenesis pathway target different U:G lesions. Mol. Immunol. 2013, 53:214-217.
61. Barnes D.E., Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet. 2004, 38:445-476.
62. Bardwell P.D., Woo C.J., Wei K., Li Z., Martin A., Sack S.Z., Parris T., Edelmann W., Scharff M.D. Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice. Nat. Immunol. 2004, 5:224-229.
63. Modrich P. Mechanisms in eukaryotic mismatch repair. J. Biol. Chem. 2006, 281:30305-30309.
64. Kadyrov F.A., Dzantiev L., Constantin N., Modrich P. Endonucleolytic function of MutLα in human mismatch repair. Cell 2006, 126:297-308.
65. Lujan S.A., Williams J.S., Clausen A.R., Clark A.B., Kunkel T.A. Ribonucleotides are signals for mismatch repair of leading-strand replication errors. Mol. Cell 2013, 50:437-443.
66. Faili A., Aoufouchi S., Gueranger Q., Zober C., Leon A., Bertocci B., Weill J.C., Reynaud C.A. AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nat. Immunol. 2002, 3:815-821.
67. Kano C., Ouchida R., Kokubo T., Wang J.Y. Rapid cell division contributes to efficient induction of A/T mutations during Ig gene hypermutation. Mol. Immunol. 2011, 48:1993-1999.
68. Milstein C., Neuberger M.S., Staden R. Both DNA strands of antibody genes are hypermutation targets. Proc. Natl. Acad. Sci. U.S.A. 1998, 95:8791-8794.
69. Rogozin I.B., Pavlov Y.I., Bebenek K., Matsuda T., Kunkel T.A. Somatic mutation hotspots correlate with DNA polymerase η error spectrum. Nat. Immunol. 2001, 2:530-536.
70. Pavlov Y.I., Rogozin I.B., Galkin A.P., Aksenova A.Y., Hanaoka F., Rada C., Kunkel T.A. Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase η during copying of a mouse immunoglobulin kappa light chain transgene. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:9954-9959.
71. 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. Mol. Cell. Biol. 2009, 29:5148-5157.
72. Unniraman S., Schatz D.G. Strand-biased spreading of mutations during somatic hypermutation. Science 2007, 317:1227-1230.