DNA Repair And Somatic Mutation In Antibody Variable Genes

抗体可变基因中的 DNA 修复和体细胞突变

• 批准号: 7592044
• 负责人: PATRICIA J GEARHART
• 金额: $ 76.89万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592044
• 关键词: Affect; Antibodies; B-Lymphocytes; Characteristics; DNA; DNA Damage; DNA Repair; DNA Repair Pathway; Dihydrofolate Reductase; Excision; Frequencies; Gene Conversion; Gene Rearrangement; Genes; Genetic; Housekeeping Gene; Hybridomas; Immunoglobulin Class Switching; Immunoglobulin Somatic Hypermutation; Immunoglobulin Switch Recombination; Immunoglobulins; Measures; Modification; Molecular; Mus; Mutation; Nucleotide Excision Repair; Process; Property; Pyrimidine Dimers; Rate; Relative (related person); Somatic Mutation; Southern Blotting; Switch Genes; System; Techniques; Time; Ultraviolet Rays; repaired

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.

免疫球蛋白可变基因经历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别转换重组。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，这些内在特征允许它们在基本DNA处理过程中进行不同的处理。 在一个实验系统中研究了这一假设，以衡量DNA修复途径（核苷酸切除修复）对可变基因和管家基因的相对效率。在小鼠杂交瘤B细胞中通过紫外线诱导DNA损伤，并通过碱性Southern印迹技术测量随时间的修复，该技术检测环丁烷嘧啶二聚体的去除。在重排的可变基因，VHS 107，DNA修复率进行了比较，在二氢叶酸还原酶基因。虽然这两个基因的转录活跃，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。