Eto Tomonori, Kinoshita Kazuo, Yoshikawa Kiyotsugu, Muramatsu Masamichi, Honjo Tasuku
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12895-8. doi: 10.1073/pnas.2135587100. Epub 2003 Oct 14.
Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID). A recent report showing induction of DNA mutations in Escherichia coli by overexpression of AID, Apobec-1, and related members of the RNA-editing cytidine deaminase family suggested that they may directly modify deoxycytidine in DNA in mammalian cells (DNA-editing model). We therefore examined whether Apobec-1 bona fide RNA-editing enzyme could show somatic hypermutation and class switching activities in murine B lymphocytes and fibroblasts. Unlike AID, Apobec-1 was unable to induce somatic hypermutation or class switching. The results force a reevaluation of the physiological significance of the DNA deaminase activities of AID and Apobec-1 in E. coli and in vitro.
通过体细胞高频突变、基因转换和类别转换重组实现的抗体多样化完全依赖于激活诱导的胞苷脱氨酶（AID）。最近一份报告显示，通过过表达AID、载脂蛋白B mRNA编辑酶1（Apobec-1）以及RNA编辑胞苷脱氨酶家族的相关成员，可在大肠杆菌中诱导DNA突变，这表明它们可能直接修饰哺乳动物细胞DNA中的脱氧胞苷（DNA编辑模型）。因此，我们研究了真正的RNA编辑酶Apobec-1是否能在小鼠B淋巴细胞和成纤维细胞中表现出体细胞高频突变和类别转换活性。与AID不同，Apobec-1无法诱导体细胞高频突变或类别转换。这些结果促使人们重新评估AID和Apobec-1在大肠杆菌及体外的DNA脱氨酶活性的生理意义。
