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, Δgcn5 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.
Highlights
DNA replication in Saccharomyces cerevisiae initiates at discrete origins referred to as Autonomously Replicating Sequences (ARS)
We propose that GCN5 acts as a positive regulator of DNA replication by counteracting the inhibitory effect of Histone Deacetylases
In the present study we have compared the effects on DNA replication of deletions of HAT1, SAS2, SAS3, GCN5 and RTT109 and mutations in the essential ESA1 gene
Summary
DNA replication in Saccharomyces cerevisiae initiates at discrete origins referred to as Autonomously Replicating Sequences (ARS). In S phase these complexes are activated by protein kinases to initiate DNA replication [1]. It is granted that histone acetylation can play a key role in the regulation of origins of DNA replication [2,3]. Convincing evidence has shown that in S.cerevisiae two major HistoneDeACetylases (HDAC), RPD3 and SIR2, act as negative regulators of origins [4,5,6,7]. A link between histone deacetylation by Rpd3p and negative impact on origin activity has been proposed in Drosophila [8]. Another HDAC, HST1, surprisingly acted as a stimulator of certain origins [9] suggesting a more complex cross-talk between histone acetylation and replication. The prevailing notion is that deacetylation of histones has a negative impact on origin activity [3]
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