GCN5 Is a Positive Regulator of Origins of DNA Replication in Saccharomyces Cerevisiae

PLoS One. 2010 Jan 29;5(1):e8964. doi: 10.1371/journal.pone.0008964.

Abstract

GCN5 encodes one of the non-essential Histone Acetyl Transferases in Saccharomyces cerevisiae. Extensive evidence has indicated that GCN5 is a key regulator of gene expression and could also be involved in transcriptional elongation, DNA repair and centromere maintenance. Here we show that the deletion of GCN5 decreases the stability of mini-chromosomes; that the tethering of Gcn5p to a crippled origin of replication stimulates its activity; that high dosage of GCN5 suppresses conditional phenotypes caused by mutant alleles of bona fide replication factors, orc2-1, orc5-1 and mcm5-461. Furthermore, Gcn5p physically associates with origins of DNA replication, while its deletion leads to localized condensation of chromatin at origins. Finally, Deltagcn5 cells display a deficiency in the assembly of pre-replicative complexes. We propose that GCN5 acts as a positive regulator of DNA replication by counteracting the inhibitory effect of Histone Deacetylases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Immunoprecipitation
  • Chromosomes, Fungal
  • DNA Replication / physiology*
  • Gene Dosage
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / physiology*
  • Plasmids
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*

Substances

  • Saccharomyces cerevisiae Proteins
  • GCN5 protein, S cerevisiae
  • Histone Acetyltransferases