Refining the Neuberger model: Uracil processing by activated B cells

European Journal of Immunology

Volumn 44, Issue 7, 2014, Pages 1913-1916

  Maul, Robert W ^a   Gearhart, Patricia J ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Class switch recombination; DNA repair; SMUG1; Somatic hypermutation; UNG

Indexed keywords

CLASS SWITCH RECOMBINATION; DNA REPAIR; SMUG1; SOMATIC HYPERMUTATION; UNG;

ANIMALS; IMMUNOGLOBULIN CLASS SWITCHING; MUTATION; URACIL; URACIL-DNA GLYCOSIDASE;

EID: 84904391374     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201444813     Document Type: Editorial

References (28)

1. Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y. and 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. et al., Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000. 102: 565-575.
3. Maul, R. W., Saribasak, H., Martomo, S. A., McClure, R. L., Yang, W., Vaisman, A., Gramlich, H. S. et al., Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat. Immunol. 2011. 12: 70-76.
4. Petersen-Mahrt, S. K., Harris, R. S. and Neuberger, M. S., AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 2002. 418: 99-103.
5. Chahwan, R., Edelmann, W., Scharff, M. D. and Roa, S., AIDing antibody diversity by error-prone mismatch repair. Semin Immunol. 2012. 24: 293-300.
6. Jiricny, J., The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 2006. 7: 335-346.
7. Modrich, P., Mechanisms in eukaryotic mismatch repair. J. Biol. Chem. 2006. 281: 30305-30309.
8. Zeng, X., Winter, D. B., Kasmer, C., Kraemer, K. H., Lehmann, A. R. and Gearhart, P. J., DNA polymerase eta is an A-T mutator in somatic hypermutation of immunoglobulin variable genes. Nat. Immunol. 2001. 2: 537-541.
9. Martomo, S. A., Yang, W. W., Wersto, R. P., Ohkumo, T., Kondo, Y., Yokoi, M., Masutani, C. et al., Different mutation signatures in DNA polymerase eta- and MSH6-deficient mice suggest separate roles in antibody diversification. Proc. Natl. Acad. Sci. USA 2005. 102: 8656-8661.
10. Delbos, F., De Smet, A., Faili, A., Aoufouchi, S., Weill, J. C. and Reynaud, C. A., Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse. J. Exp. Med. 2005. 201: 1191-1196.
11. Saribasak, H., Maul, R. W., Cao, Z., Yang, W. W., Schenten, D., Kracker, S. and Gearhart, P. J., DNA polymerase zeta generates tandem mutations in immunoglobulin variable regions. J. Exp. Med. 2012. 209: 1075-1081.
12. Langerak, P., Nygren, A. O., Krijger, P. H., van den Berk, P. C. and Jacobs, H., A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification. J. Exp. Med. 2007. 204: 1989-1998.
13. Saribasak, H. and Gearhart, P. J., Does DNA repair occur during somatic hypermutation? Semin. Immunol. 2012. 24: 287-292.
14. Di Noia, J. and Neuberger, M. S., Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002. 419: 43-48.
15. Rada, C., Williams, G. T., Nilsen, H., Barnes, D. E., Lindahl, T. and Neuberger, M. S., Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr. Biol. 2002. 12: 1748-1755.
16. Krokan, H. E., Saetrom, P., Aas, P. A., Pettersen, H. S., Kavli, B. and Slupphaug, G., Error-free versus mutagenic processing of genomic uracil-relevance to cancer. DNA Repair (Amst) 2014. 19: 38-47.
17. Jansen, J. G., Langerak, P., Tsaalbi-Shtylik, A., van den Berk, P., Jacobs, H. and de Wind, N., Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice. J. Exp. Med. 2006. 203: 319-323.
18. Saribasak, H., Maul, R. W., Cao, Z., McClure, R. L., Yang, W., McNeill, D. R., Wilson, D. M., 3rd et al., XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes. J. Exp. Med. 2011. 208: 2209-2216.
19. Wu, X. and Stavnezer, J., DNA polymerase beta 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.
20. Di Noia, J. M., Rada, C. and Neuberger, M. S., SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair. EMBO J. 2006. 25: 585-595.
21. Rada, C., Di Noia, J. M. and 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.
22. Dingler, F. A., Kemmerich, K., Neuberger, M. S. and Rada, C., Uracil excision by endogenous SMUG1 glycosylase promotes efficient Ig class switching and impacts A:T substitutions during somatic mutation. Eur. J. Immunol. 2014. 44: 1925-1935.
23. Krijger, P. H., Langerak, P., van den Berk, P. C. and Jacobs, H., Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation. J. Exp. Med. 2009. 206: 2603-2611.
24. Frieder, D., Larijani, M., Collins, C., Shulman, M. and Martin, A., The concerted action of Msh2 and UNG stimulates somatic hypermutation at A.T base pairs. Mol. Cell Biol. 2009. 29: 5148-5157.
25. Zivojnovic, M., Delbos, F., Girelli Zubani, G., Jule, A., Alcais, A., Weill, J. C., Reynaud, C. A. et al. Somatic hypermutation at A/T-Rich oligonucleotide substrates shows different strand polarities in Ung-deficient or -proficient backgrounds. Mol. Cell. Biol. 2014. 34: 2176-2187.
26. Hagen, L., Kavli, B., Sousa, M. M., Torseth, K., Liabakk, N. B., Sundheim, O., Pena-Diaz, J. et al., Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA. EMBO J. 2008. 27: 51-61.
27. Sharbeen, G., Yee, C. W., Smith, A. L. and 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.
28. Faili, A., Aoufouchi, S., Gueranger, Q., Zober, C., Leon, A., Bertocci, B., Weill, J. C. et al., AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nat. Immunol. 2002. 3: 815-821.