Molecular mechanism of assembly and control of mammalian replication factories

点击翻译按钮获取中文摘要

To understand molecular mechanism of mammalian DNA replication, I have focused on mouse DNA polymerase alpha. According to extensive analysis of DNA polymerase alpha,1) we developed a novel potent inhibitor for mammalian DNA polymerase alpha, from derivatives of dehydroaltenusin. Using this novel inhibitor, we discussed that uncoupling of leading strand synthesis and lagging strand synthesis caused aberrant RPA foci in mammalian nucleus in NIH3T3 cells. 2) Characterization of temperature-sensitive mutant cell line which has mutation in DNA polymerase alpha, suggested novel nuclear protein quality control mechanism to eliminate aberrant proteins from nucleus. In this quality control mechanism involves HSP90 and PA28gamma. 3) Interaction between DNA polymerase alpha and pot1 revealed intrinsically disordered region of DNA polymerase alpha serves as molecular binding site for chromatin binding protein which contains typical OB-fold containing proteins such as RPA, Mcm10, pot1, CST complex.