Martomo Stella A, Gearhart Patricia J
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Curr Opin Immunol. 2006 Jun;18(3):243-8. doi: 10.1016/j.coi.2006.03.007. Epub 2006 Apr 17.
Somatic hypermutation generates high-affinity antibodies of different isotypes that efficiently protect us against a plethora of pathogens. Recent analyses of the types of mutations produced in gene-deficient mice have indicated how DNA repair proteins are drawn into the pathway. Activation-induced cytosine deaminase begins the process by deaminating cytosine to uracil in DNA. The uracils are then recognized by the base excision repair protein uracil DNA glycosylase and by the mismatch repair proteins MutS homologue 2 and MutS homologue 6. Instead of repairing the uracils, these proteins attract low fidelity DNA polymerases, which synthesize nucleotide substitutions at an unprecedented level.
体细胞高频突变产生不同同种型的高亲和力抗体，能有效保护我们抵御多种病原体。最近对基因缺陷小鼠中产生的突变类型的分析表明了DNA修复蛋白是如何被纳入该途径的。激活诱导的胞嘧啶脱氨酶通过将DNA中的胞嘧啶脱氨为尿嘧啶来启动这一过程。然后，尿嘧啶被碱基切除修复蛋白尿嘧啶DNA糖基化酶以及错配修复蛋白MutS同源物2和MutS同源物6识别。这些蛋白并未修复尿嘧啶，而是吸引低保真度的DNA聚合酶，后者以前所未有的水平合成核苷酸替换。
