Structure-Function Studies Of DNA Replication Fidelity

今年，我们的团队发表了四篇与DNA复制及其保真度相关的科学文章。我们发现，DNA聚合酶δ在断裂诱导的染色体末端复制过程中，在前导链和滞后链的复制中都起着主导作用。我们发现，DNA聚合酶δ在起始和终止过程中的前导链DNA复制中也有关键作用。我们发现，在线粒体DNA复制过程中，缺失突变以显著的频率形成，该频率通过复制DNA聚合酶Pol γ中的疾病相关突变而强烈增加。我们解决了有史以来第一个X射线晶体结构的DNA聚合酶亩执行掺入一个真正的双链DNA断裂相关的非同源末端连接这样的断裂。

This year, our group published four scientific articles related to DNA replication and its fidelity. We showed that DNA polymerase delta has the predominant role in replication both the leading and the lagging strand during break-induced replication of chromosome ends. We showed that DNA polymerase delta also has key roles in leading strand DNA replication during initiation and during termination. We showed that during mitochondrial DNA replication, deletion mutations are formed at a significant frequency that is strongly increased by disease-associated mutations in the replicative DNA polymerase, Pol gamma. We solved the first ever X-ray crystal structure of DNA polymerase mu performing incorporation of a true double-strand DNA break relevant to nonhomologous end-joining of such breaks.