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真核复制体的关键组成部分 GINS 复合物的结构与功能。

Structure and function of the GINS complex, a key component of the eukaryotic replisome.

机构信息

Biomedical Sciences Research Complex, School of Biology, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.

出版信息

Biochem J. 2010 Jan 15;425(3):489-500. doi: 10.1042/BJ20091531.

DOI:10.1042/BJ20091531
PMID:20070258
Abstract

High-fidelity chromosomal DNA replication is fundamental to all forms of cellular life and requires the complex interplay of a wide variety of essential and non-essential protein factors in a spatially and temporally co-ordinated manner. In eukaryotes, the GINS complex (from the Japanese go-ichi-ni-san meaning 5-1-2-3, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3) was recently identified as a novel factor essential for both the initiation and elongation stages of the replication process. Biochemical analysis has placed GINS at the heart of the eukaryotic replication apparatus as a component of the CMG [Cdc45-MCM (minichromosome maintenance) helicase-GINS] complex that most likely serves as the replicative helicase, unwinding duplex DNA ahead of the moving replication fork. GINS homologues are found in the archaea and have been shown to interact directly with the MCM helicase and with primase, suggesting a central role for the complex in archaeal chromosome replication also. The present review summarizes current knowledge of the structure, function and evolution of the GINS complex in eukaryotes and archaea, discusses possible functions of the GINS complex and highlights recent results that point to possible regulation of GINS function in response to DNA damage.

摘要

高保真染色体 DNA 复制是所有形式的细胞生命的基础,需要广泛的必需和非必需蛋白质因子以空间和时间协调的方式进行复杂的相互作用。在真核生物中,GINS 复合物(来自日语 go-ichi-ni-san,意为 5-1-2-3,是复合物 Sld5、Psf1、Psf2 和 Psf3 的四个相关亚基)最近被确定为复制过程的起始和延伸阶段所必需的新型因子。生化分析将 GINS 定位在真核复制装置的核心,作为 CMG(Cdc45-MCM [微小染色体维持] 解旋酶-GINS)复合物的一个组成部分,该复合物很可能作为复制解旋酶,在移动的复制叉前解开双链 DNA。在古菌中发现了 GINS 同源物,并已证明其与 MCM 解旋酶和引物酶直接相互作用,表明该复合物在古菌染色体复制中也具有核心作用。本综述总结了目前对真核生物和古菌中 GINS 复合物的结构、功能和进化的了解,讨论了 GINS 复合物的可能功能,并强调了最近的结果,这些结果表明 GINS 功能可能会响应 DNA 损伤而受到调节。

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