Protein Interactions in Antibody Diversity

抗体多样性中的蛋白质相互作用

• 批准号: 8552453
• 负责人: PATRICIA J GEARHART
• 金额: $ 53.9万
• 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/8552453
• 关键词: Amino Acids; Antibody Affinity; Antibody Diversity; DNA polymerase zeta; DNA strand break; DNA-Directed DNA Polymerase; Data; Genes; Immunoglobulin Somatic Hypermutation; MSH2 gene; MSH6 gene; Mus; Mutation; Pathway interactions; Polymerase; Proteins; Testing; repaired

We have identified a unique signature for DNA polymerase zeta which is to generate tandem mutations druing somatic hypermutation. Using mice deficient for various polymerases, we observed that polymerase eta is a dominant protein, and the effect of polymerase zeta was more pronounced in the absence of polymerase eta. Furthermore, data sugest that polymerase zeta functions in the MSH2-MSH6 pathway. An advantage to using polymerase zeta to inroduce tandem mutations would be to efficiently change amino acids in variable genes to generate higher affinity antibodies.

我们已经确定了DNA聚合酶zeta的一个独特的签名，它是在体细胞超突变过程中产生串联突变。使用缺乏各种聚合酶的小鼠，我们观察到聚合酶eta是一种主要蛋白质，聚合酶eta的作用在缺乏聚合酶eta的情况下更加明显。此外，数据表明聚合酶zeta在MSH 2-MSH 6途径中起作用。使用聚合酶ζ引入串联突变的优点是有效地改变可变基因中的氨基酸以产生更高亲和力的抗体。