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人类GINS复合物与Cdc45和MCM相关联,对DNA复制至关重要。

The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.

作者信息

Aparicio Tomás, Guillou Emmanuelle, Coloma Javier, Montoya Guillermo, Méndez Juan

机构信息

DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.

出版信息

Nucleic Acids Res. 2009 Apr;37(7):2087-95. doi: 10.1093/nar/gkp065. Epub 2009 Feb 17.

Abstract

The GINS complex, originally discovered in Saccharomyces cerevisiae and Xenopus laevis, binds to DNA replication origins shortly before the onset of S phase and travels with the replication forks after initiation. In this study we present a detailed characterization of the human GINS (hGINS) homolog. Using new antibodies that allow the detection of endogenous hGINS in cells and tissues, we have examined its expression, abundance, subcellular localization and association with other DNA replication proteins. Expression of hGINS is restricted to actively proliferating cells. During the S phase, hGINS becomes part of a Cdc45-MCM-GINS (CMG) complex that is assembled on chromatin. Down-regulation of hGINS destabilizes CMG, causes a G1-S arrest and slows down ongoing DNA replication, effectively blocking cell proliferation. Our data support the notion that hGINS is an essential component of the human replisome.

摘要

GINS复合体最初是在酿酒酵母和非洲爪蟾中发现的,在S期开始前不久与DNA复制起点结合,并在起始后随复制叉移动。在本研究中,我们对人类GINS(hGINS)同源物进行了详细表征。使用能够检测细胞和组织中内源性hGINS的新抗体,我们检测了其表达、丰度、亚细胞定位以及与其他DNA复制蛋白的关联。hGINS的表达仅限于活跃增殖的细胞。在S期,hGINS成为组装在染色质上的Cdc45-MCM-GINS(CMG)复合体的一部分。hGINS的下调会使CMG不稳定,导致G1-S期阻滞并减缓正在进行的DNA复制,有效阻断细胞增殖。我们的数据支持hGINS是人类复制体重要组成部分的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc52/2673421/3907f23934b3/gkp065f1.jpg

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