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AID to overcome the limitations of genomic information

Nature Immunology volume 6, pages 655–661 (2005)Cite this article

Abstract

The limitations of genomic information forced our ancestors to adopt a strategy for introducing somatic DNA alterations with the risk of genome instability. Although activation-induced deaminase (AID) is involved in DNA cleavage in somatic hypermutation and class-switch recombination, its mechanism of action has been debated extensively, with the two main hypotheses being distinguished by the chief target of AID: RNA or DNA. The principle distinction between the two hypotheses is the requirement for translation of edited mRNA or uracil removal from DNA for DNA cleavage. Although a series of experiments has provided support for the 'RNA-editing' hypothesis and requires reevaluation of the 'DNA-deamination' hypothesis, definitive proof is yet to come.

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Figure 1: RNA-editing and DNA-deamination models.
Figure 2: Functions of UNG and MSH2 in CSR.
Figure 3: Association of AID with CSR- and SHM-specific cofactors.

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Acknowledgements

We thank S. Fagarasan, T. Okazaki, M. Nishikori, D. Yabe, N. Yamamoto, N. Begum, A. Kotani, I. Okazaki, J. Wang for critical reading of the manuscript, and Y. Shiraki and T. Nishikawa for support in preparing the manuscript. Supported by the Ministry of Education, Science, Sports, and Culture of Japan (Center of Excellence 12CE2006).

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  1. Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto, 606-8501, Japan

    Tasuku Honjo, Hitoshi Nagaoka, Reiko Shinkura & Masamichi Muramatsu

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Correspondence to Tasuku Honjo.

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Honjo, T., Nagaoka, H., Shinkura, R. et al. AID to overcome the limitations of genomic information. Nat Immunol 6, 655–661 (2005). https://doi.org/10.1038/ni1218

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