O'Donnell Mike, Li Huilin
DNA Replication Lab, The Rockefeller University, 1230 York Avenue, New York, New York, USA; Howard Hughes Medical Institute.
Department of Biochemistry & Cell Biology, Stony Brook University, Stony Brook, New York, USA; Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
Curr Biol. 2016 Mar 21;26(6):R247-56. doi: 10.1016/j.cub.2016.02.034.
The machinery at the eukaryotic replication fork has seen many new structural advances using electron microscopy and crystallography. Recent structures of eukaryotic replisome components include the Mcm2-7 complex, the CMG helicase, DNA polymerases, a Ctf4 trimer hub and the first look at a core replisome of 20 different proteins containing the helicase, primase, leading polymerase and a lagging strand polymerase. The eukaryotic core replisome shows an unanticipated architecture, with one polymerase sitting above the helicase and the other below. Additionally, structures of Mcm2 bound to an H3/H4 tetramer suggest a direct role of the replisome in handling nucleosomes, which are important to DNA organization and gene regulation. This review provides a summary of some of the many recent advances in the structure of the eukaryotic replisome.
利用电子显微镜和晶体学技术,真核生物复制叉处的机制取得了许多新的结构进展。真核生物复制体组件的最新结构包括Mcm2-7复合体、CMG解旋酶、DNA聚合酶、Ctf4三聚体枢纽,以及首次观察到的由20种不同蛋白质组成的核心复制体,其中包含解旋酶、引发酶、前导链聚合酶和后随链聚合酶。真核生物核心复制体呈现出一种意想不到的结构,一种聚合酶位于解旋酶上方,另一种位于下方。此外,与H3/H4四聚体结合的Mcm2结构表明,复制体在处理核小体方面具有直接作用,而核小体对DNA组织和基因调控很重要。本综述总结了真核生物复制体结构近期众多进展中的一些内容。