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

被引：85
|
作者：
Aparicio, Toms [1 ]
Guillou, Emmanuelle [1 ]
Coloma, Javier [2 ]
Montoya, Guillermo [2 ]
Mendez, Juan [1 ]
机构：
[1] Spanish Natl Canc Res Ctr CNIO, Mol Oncol Programme, DNA Replicat Grp, E-28029 Madrid, Spain
[2] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Programme, Macromol Crystallog Grp, E-28029 Madrid, Spain
来源：
NUCLEIC ACIDS RESEARCH | 2009年 / 37卷 / 07期
关键词：
EUKARYOTIC DNA; BUDDING YEAST; MULTIPROTEIN COMPLEX; CRYSTAL-STRUCTURE; CELL-CYCLE; IN-VIVO; S-PHASE; PROGRESSION; PROTEINS; FORKS;
D O I：
10.1093/nar/gkp065
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 Cdc45MCMGINS (CMG) complex that is assembled on chromatin. Down-regulation of hGINS destabilizes CMG, causes a G1S 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.
引用
收藏
页码：2087 / 2095
页数：9
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