Honjo Tasuku, Nagaoka Hitoshi, Shinkura Reiko, Muramatsu Masamichi
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501 Japan.
Nat Immunol. 2005 Jul;6(7):655-61. doi: 10.1038/ni1218.
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.
基因组信息的局限性迫使我们的祖先采取一种引入体细胞DNA改变的策略,但这存在基因组不稳定的风险。尽管激活诱导脱氨酶(AID)参与体细胞超突变和类别转换重组中的DNA切割,但其作用机制一直存在广泛争议,两种主要假说的区别在于AID的主要作用靶点:RNA还是DNA。这两种假说的主要区别在于DNA切割是需要编辑后的mRNA进行翻译还是从DNA上去除尿嘧啶。尽管一系列实验为“RNA编辑”假说提供了支持,需要对“DNA脱氨基”假说进行重新评估,但确凿的证据尚未出现。