重组激活基因在抗原受体多样性产生中的作用及其他。
Role of recombination activating genes in the generation of antigen receptor diversity and beyond.
机构信息
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India.
出版信息
Immunology. 2012 Dec;137(4):271-81. doi: 10.1111/imm.12009.
Abstract
V(D)J recombination is the process by which antibody and T-cell receptor diversity is attained. During this process, antigen receptor gene segments are cleaved and rejoined by non-homologous DNA end joining for the generation of combinatorial diversity. The major players of the initial process of cleavage are the proteins known as RAG1 (recombination activating gene 1) and RAG2. In this review, we discuss the physiological function of RAGs as a sequence-specific nuclease and its pathological role as a structure-specific nuclease. The first part of the review discusses the basic mechanism of V(D)J recombination, and the last part focuses on how the RAG complex functions as a sequence-specific and structure-specific nuclease. It also deals with the off-target cleavage of RAGs and its implications in genomic instability.
摘要
V(D)J 重组是获得抗体和 T 细胞受体多样性的过程。在这个过程中，抗原受体基因片段通过非同源 DNA 末端连接被切割和重新连接，从而产生组合多样性。最初切割过程的主要参与者是称为 RAG1（重组激活基因 1）和 RAG2 的蛋白质。在这篇综述中，我们讨论了 RAG 作为序列特异性核酸内切酶的生理功能及其作为结构特异性核酸内切酶的病理作用。综述的第一部分讨论了 V(D)J 重组的基本机制，最后一部分重点介绍了 RAG 复合物如何作为序列特异性和结构特异性核酸内切酶发挥作用。它还涉及 RAG 的非靶标切割及其对基因组不稳定性的影响。
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