4.8 Article

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

Journal

NUCLEIC ACIDS RESEARCH
Volume 37, Issue 7, Pages 2087-2095

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp065

Keywords

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Funding

  1. Spanish Ministry of Science and Innovation [BFU-04886, CSD2007-0015]
  2. 'Ramon y Cajal' [BFU2008-01344]
  3. European Union [MC IRG FP6-031129, LSHG-CT-2005-512028]
  4. Fundacion Caja Madrid
  5. Fondation Recherche Medicale, France
  6. Spanish Ministry of Science and Innovation

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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.

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