DNA Repair And Somatic Mutation In Antibody Variable Genes

免疫球蛋白可变基因经历了几种不寻常的遗传修饰以产生多样性，如基因重排、基因转换、体细胞超突变和重链类开关重组。鉴于这些专门的过程，我们研究了可变基因具有内在特征的可能性，这些特征允许它们在基本DNA交易过程中以不同的方式进行处理。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-对一个可变基因和一个管家基因的相对效率。用紫外光诱导小鼠杂交瘤B细胞DNA损伤，用碱性Southern印迹技术检测环丁烷嘧啶二聚体的清除，以检测修复随时间的变化。比较了重排可变基因VHS107和二氢叶酸还原酶基因的DNA修复速率。虽然这两个基因都被活跃地转录，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属性。

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.