Molecular Mechanism of Chromosomal DNA Replication Apparatus

点击翻译按钮获取中文摘要

In order to understand the molecular mechanism of eukaryotic chromosomal DNA replication, this project has been focussing on elucidating the molecular mechanism of formation of the replication apparatus in various eukaryotic systems including yeast, Xenopus eggs, Drosophila, mouse and human cells. In particular, we extensively studied how both the lagging strand and leading strand synthesis complexes are formed. In the course of these studies, we identified several new replication proteins interacting with DNA polymerase epsilon which might be a leading strand polymerase. Furthermore, we purified yeast Cdc7/Dbf4 protein kinase and human Mcm2-7 protein complex both of which participates in the initiation and elongation step of chromosomal DNA replication. From these studies, we found that Cdc7/Dbf4 protein kinase activity is regulated by Rad53 protein kinase that participates in both S- and DNA damage checkpoint and the subcomplex of human Mcm2-7 proteins has a DNA helicase activity, suggesting that the complex is a DNA helicase which functions at the replication fork.