The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.
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.
Aparicio
Tomás
T
DNA Replication Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Guillou
Emmanuelle
E
Coloma
Javier
J
Montoya
Guillermo
G
Méndez
Juan
J
D000906:Antibodies; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology / Q000378:metabolism*; D004261:DNA Replication; D006801:Humans; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D016196:S Phase / Q000235:genetics
D000906:Antibodies; C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D021122:Protein Subunits