Martinez Matthew P, Wacker Amanda L, Bruck Irina, Kaplan Daniel L
Department of Biomedical Sciences, Florida State University College of Medicine, 1115 W. Call St., Tallahassee, FL 32306, USA.
Genes (Basel). 2017 Apr 6;8(4):117. doi: 10.3390/genes8040117.
The replicative helicase unwinds parental double-stranded DNA at a replication fork to provide single-stranded DNA templates for the replicative polymerases. In eukaryotes, the replicative helicase is composed of the Cdc45 protein, the heterohexameric ring-shaped Mcm2-7 complex, and the tetrameric GINS complex (CMG). The CMG proteins bind directly to DNA, as demonstrated by experiments with purified proteins. The mechanism and function of these DNA-protein interactions are presently being investigated, and a number of important discoveries relating to how the helicase proteins interact with DNA have been reported recently. While some of the protein-DNA interactions directly relate to the unwinding function of the enzyme complex, other protein-DNA interactions may be important for minichromosome maintenance (MCM) loading, origin melting or replication stress. This review describes our current understanding of how the eukaryotic replicative helicase subunits interact with DNA structures in vitro, and proposed models for the in vivo functions of replicative helicase-DNA interactions are also described.
复制解旋酶在复制叉处解开亲代双链DNA,为复制聚合酶提供单链DNA模板。在真核生物中,复制解旋酶由Cdc45蛋白、异源六聚体环状Mcm2 - 7复合物和四聚体GINS复合物(CMG)组成。如纯化蛋白实验所示,CMG蛋白直接与DNA结合。目前正在研究这些DNA - 蛋白质相互作用的机制和功能,最近已有许多关于解旋酶蛋白如何与DNA相互作用的重要发现报道。虽然一些蛋白质 - DNA相互作用直接与酶复合物的解旋功能相关,但其他蛋白质 - DNA相互作用可能对微型染色体维持(MCM)加载、起始点解链或复制应激很重要。本综述描述了我们目前对真核生物复制解旋酶亚基如何在体外与DNA结构相互作用的理解,还描述了复制解旋酶 - DNA相互作用在体内功能的推测模型。