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Current insights into the mechanism of mammalian immunoglobulin class switch recombination.
Critical Reviews in Biochemistry and Molecular Biology ( IF 6.2 ) Pub Date : 2019-09-11 , DOI: 10.1080/10409238.2019.1659227
Kefei Yu 1 , Michael R Lieber 2, 3, 4, 5
Affiliation  

Immunoglobulin (Ig) class switch recombination (CSR) is the gene rearrangement process by which B lymphocytes change the Ig heavy chain constant region to permit a switch of Ig isotype from IgM to IgG, IgA, or IgE. At the DNA level, CSR occurs via generation and joining of DNA double strand breaks (DSBs) at intronic switch regions located just upstream of each of the heavy chain constant regions. Activation-induced deaminase (AID), a B cell specific enzyme, catalyzes cytosine deaminations (converting cytosines to uracils) as the initial DNA lesions that eventually lead to DSBs and CSR. Progress on AID structure integrates very well with knowledge about Ig class switch region nucleic acid structures that are supported by functional studies. It is an ideal time to review what is known about the mechanism of Ig CSR and its relation to somatic hypermutation. There have been many comprehensive reviews on various aspects of the CSR reaction and regulation of AID expression and activity. This review is focused on the relation between AID and switch region nucleic acid structures, with a particular emphasis on R-loops.



中文翻译:


目前对哺乳动物免疫球蛋白类别转换重组机制的见解。



免疫球蛋白 (Ig) 类别转换重组 (CSR) 是 B 淋巴细胞改变 Ig 重链恒定区以允许 Ig 同种型从 IgM 转换为 IgG、IgA 或 IgE 的基因重排过程。在 DNA 水平上,CSR 通过在位于每个重链恒定区上游的内含子开关区域产生和连接 DNA 双链断裂 (DSB) 来发生。激活诱导脱氨酶 (AID) 是一种 B 细胞特异性酶,催化胞嘧啶脱氨(将胞嘧啶转化为尿嘧啶)作为最初的 DNA 损伤,最终导致 DSB 和 CSR。 AID 结构的进展与功能研究支持的 Ig 类开关区核酸结构的知识很好地结合在一起。现在是回顾 Ig CSR 机制及其与体细胞超突变关系的理想时机。关于 CSR 反应以及 AID 表达和活性调节的各个方面已有许多全面的综述。本综述的重点是 AID 和开关区核酸结构之间的关系,特别强调 R 环。

更新日期:2019-09-11
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