体细胞高频突变过程中会发生 DNA 修复吗？
Does DNA repair occur during somatic hypermutation?
机构信息
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States.
出版信息
Semin Immunol. 2012 Aug;24(4):287-92. doi: 10.1016/j.smim.2012.05.002. Epub 2012 Jun 22.
Abstract
Activation-induced deaminase (AID) initiates a flood of DNA damage in the immunoglobulin loci, leading to abasic sites, single-strand breaks and mismatches. It is compelling that some proteins in the canonical base excision and mismatch repair pathways have been hijacked to increase mutagenesis during somatic hypermutation. Thus, the AID-induced mutagenic pathways involve a mix of DNA repair proteins and low fidelity DNA polymerases to create antibody diversity. In this review, we analyze the roles of base excision repair, mismatch repair, and mutagenesis during somatic hypermutation of rearranged variable genes. The emerging view is that faithful base excision repair occurs simultaneously with mutagenesis, whereas faithful mismatch repair is mostly absent.
摘要
激活诱导的脱氨酶（AID）在免疫球蛋白基因座中引发大量 DNA 损伤，导致碱基缺失、单链断裂和错配。令人信服的是，经典碱基切除和错配修复途径中的一些蛋白质已被劫持，以增加体细胞超突变过程中的突变率。因此，AID 诱导的突变途径涉及 DNA 修复蛋白和低保真度 DNA 聚合酶的混合，以产生抗体多样性。在这篇综述中，我们分析了碱基切除修复、错配修复和体细胞超突变过程中重排可变基因的突变作用。新出现的观点是，忠实的碱基切除修复与突变同时发生，而忠实的错配修复则大部分缺失。
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