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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Proliferation
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / immunology
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Replication*
  • Humans
  • Protein Subunits / immunology
  • Protein Subunits / metabolism
  • S Phase / genetics

Substances

  • Antibodies
  • CDC45 protein, human
  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Protein Subunits