STUDIES OF IMMUNOGLOBULIN GENE REARRANGEMENT

免疫球蛋白基因重排的研究

• 批准号: 3776322
• 负责人: M GELLERT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 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/3776322
• 关键词: T cell receptor; gene rearrangement; genetic models; immunoglobulin genes; laboratory mouse; nucleic acid structure

Our earlier work on antigen receptor gene rearrangement (V(D)J recombination) described one type of broken DNA molecules that were plausible intermediates in this process. These molecules, seen at the T cell receptor delta locus (TCR), had only the free end containing the recombination signal sequence. We have now also been able to find broken molecules with the end of the coding sequence, but only in DNA from mice with the scid mutation, which interferes with the joining of these ends. The coding ends are found to have an abnormal structure: the two DNA strands are linked to each other in a hairpin configuration.The presence of hairpins offers a good explanation for the observation, in immunoglobulin and T cell receptor coding junctions, of self- complementary sequences formed during recombination. If a hairpin structure is nicked off-center, a self- complementary insertion will naturally result. These results strengthen the evidence for a breakage-reunion model of V(D)J recombination, but also indicate that the process must be different from earlier examples of this type.

我们早期在抗原受体基因重排(V(D)J)方面的工作 重组)描述了一种类型的断裂DNA分子 这一过程中看似合理的中间体。这些分子，在 T细胞受体德尔塔基因(TCR)，只有含有 复合信号序列。 我们现在也已经能够找到断裂的分子与末端的 编码序列，但仅在带有SCID突变的小鼠的DNA中，这是 干扰这些末端的连接。发现编码末端为 有一种不正常的结构：两条DNA链相互连接 在发夹结构中。发夹的存在提供了一个很好的 对观察到的免疫球蛋白和T细胞受体的解释 自互补序列的编码连接，形成于 重组。如果发夹结构偏离中心，则自身 互补插入自然会产生。 这些结果加强了对破损-再结合模型的支持。 V(D)J重组，但也表明该过程必须 与早期的这种类型的例子不同。