Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
PLoS One. 2010 Jan 29;5(1):e8964. doi: 10.1371/journal.pone.0008964.
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.
GCN5 编码酿酒酵母中非必需的组蛋白乙酰转移酶之一。大量证据表明，GCN5 是基因表达的关键调节剂，也可能参与转录延伸、DNA 修复和着丝粒维持。在这里，我们表明 GCN5 的缺失会降低微型染色体的稳定性；将 Gcn5p 固定在受损的复制起点上会刺激其活性；高剂量的 GCN5 可抑制由 bona fide 复制因子突变等位基因引起的条件表型，如 orc2-1、orc5-1 和 mcm5-461。此外，Gcn5p 与 DNA 复制起点物理结合，而其缺失会导致染色质在起点处局部浓缩。最后，Deltagcn5 细胞在前复制复合物的组装中表现出缺陷。我们提出，GCN5 通过抵消组蛋白去乙酰化酶的抑制作用，作为 DNA 复制的正调控因子发挥作用。
