DNA Repair And Somatic Mutation In Antibody Variable Genes

免疫球蛋白可变基因通过几种不寻常的遗传修饰来产生多样性，如基因重排、基因转换、体细胞超突变和重链类开关重组。鉴于这些特殊的过程，我们研究了可变基因具有内在特征的可能性，这些特征使它们在基本DNA交易过程中也能得到不同的处理。这一假设在一个实验系统中进行了研究，以衡量DNA修复途径（核苷酸切除修复）在可变基因和内务基因上的相对效率。紫外线诱导小鼠杂杂瘤B细胞DNA损伤，并通过碱性Southern blot技术检测环丁烷嘧啶二聚体的去除情况。将重排可变基因VHS107中的DNA修复率与二氢叶酸还原酶基因中的DNA修复率进行了比较。虽然这两个基因都有转录活性，但VHS107基因的修复效率低于二氢叶酸还原酶基因。这些结果表明，可变基因具有影响核苷酸切除修复效率的固有特性。

Immunoglobulin variable genes undergo several unusual genetic modifications to generate diversity, such as gene rearrangement, gene conversion, somatic hypermutation, and heavy chain class switch recombination. In view of these specialized processes, we examined the possibility that variable genes have intrinsic characteristics that allow them to be processed differently in the course of basic DNA transactions as well. This hypothesis was studied in an experimental system to gauge the relative efficiency of a DNA repair pathway, nucleotide excision repair, on a variable gene and a housekeeping gene. DNA damage was induced by ultraviolet light in murine hybridoma B cells, and repair was measured over time by an alkaline Southern blot technique, which detected removal of cyclobutane pyrimidine dimers. The rate of DNA repair in a rearranged variable gene, VHS107, was compared to that in the dihydrofolate reductase gene. Although both genes were actively transcribed, the VHS107 gene was repaired less efficiently than the dihydrofolate reductase gene. These results suggest that variable genes have inherent properties that affect the efficiency of nucleotide excision repair.