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真核生物复制性解旋酶亚基与DNA的相互作用及其在DNA复制中的作用。

Eukaryotic Replicative Helicase Subunit Interaction with DNA and Its Role in DNA Replication.

作者信息

Martinez Matthew P, Wacker Amanda L, Bruck Irina, Kaplan Daniel L

机构信息

Department of Biomedical Sciences, Florida State University College of Medicine, 1115 W. Call St., Tallahassee, FL 32306, USA.

出版信息

Genes (Basel). 2017 Apr 6;8(4):117. doi: 10.3390/genes8040117.

DOI:10.3390/genes8040117
PMID:28383499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5406864/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/91411a6f5d8c/genes-08-00117-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d77e3af7b1c3/genes-08-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/329f7d2dd335/genes-08-00117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d10f463c9e96/genes-08-00117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/c66171f6a194/genes-08-00117-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d3efea100df1/genes-08-00117-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/92c1100f6567/genes-08-00117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/91411a6f5d8c/genes-08-00117-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d77e3af7b1c3/genes-08-00117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/329f7d2dd335/genes-08-00117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d10f463c9e96/genes-08-00117-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/c66171f6a194/genes-08-00117-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/d3efea100df1/genes-08-00117-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/92c1100f6567/genes-08-00117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7525/5406864/91411a6f5d8c/genes-08-00117-g007.jpg

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本文引用的文献

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2
Cdc45-induced loading of human RPA onto single-stranded DNA.Cdc45诱导人源RPA加载到单链DNA上。
Nucleic Acids Res. 2017 Apr 7;45(6):3217-3230. doi: 10.1093/nar/gkw1364.
3
Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation.真核生物CMG解旋酶在复制叉处的结构及其对复制体结构和起始点引发的影响
GINS2通过MAPK/ERK信号通路影响胰腺癌细胞的细胞活力、细胞凋亡和细胞周期进程。
J Cancer. 2020 May 19;11(16):4662-4670. doi: 10.7150/jca.38386. eCollection 2020.
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Amidst multiple binding orientations on fork DNA, MCM helicase proceeds N-first for unwinding.在叉形 DNA 上的多种结合构象中,MCM 解旋酶以前向后(N-first)的方式进行解旋。
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Keap1-MCM3 interaction is a potential coordinator of molecular machineries of antioxidant response and genomic DNA replication in metazoa.Keap1-MCM3 相互作用是后生动物抗氧化反应和基因组 DNA 复制的分子机制的潜在协调者。
Sci Rep. 2018 Aug 14;8(1):12136. doi: 10.1038/s41598-018-30562-y.
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