Graduate School of Life and Environmental Sciences, Initiative for the Promotion of Young Scientists' Independent Research, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
Genes Cells. 2011 Apr;16(4):467-77. doi: 10.1111/j.1365-2443.2011.01493.x. Epub 2011 Mar 15.
The acetylation of histone H3 on lysine 56 (H3-K56) occurs during S phase and contributes to the processes of DNA damage repair and histone gene transcription. Hst3 and Hst4 have been implicated in the removal of histone H3-K56 acetylation in Saccharomyces cerevisiae. Here, we show that Hst3 and Hst4 regulate the replicative lifespan of S. cerevisiae mother cells. An hst3Δ hst4Δ double-mutant strain, in which acetylation of histone H3-K56 persists throughout the genome during the cell cycle, exhibits genomic instability, which is manifested by a loss of heterozygosity with cell aging. Furthermore, we show that in the absence of other proteins Hst3 and Hst4 can deacetylate nucleosomal histone H3-K56 in a nicotinamide adenine dinucleotide(NAD)(+) -dependent manner. Our results suggest that Hst3 and Hst4 regulate replicative lifespan through their ability to deacetylate histone H3-K56 to minimize genomic instability.
组蛋白 H3 赖氨酸 56 乙酰化（H3-K56）发生在 S 期，有助于 DNA 损伤修复和组蛋白基因转录过程。Hst3 和 Hst4 被认为参与了酿酒酵母中组蛋白 H3-K56 乙酰化的去除。在这里，我们发现 Hst3 和 Hst4 调节酿酒酵母母细胞的复制寿命。在 hst3Δ hst4Δ 双突变株中，组蛋白 H3-K56 的乙酰化在细胞周期中持续存在于整个基因组中，表现出基因组不稳定性，这表现为随着细胞衰老而失去杂合性。此外，我们发现，在没有其他蛋白质的情况下，Hst3 和 Hst4 可以以烟酰胺腺嘌呤二核苷酸（NAD）依赖性方式去乙酰化核小体组蛋白 H3-K56。我们的结果表明，Hst3 和 Hst4 通过去乙酰化组蛋白 H3-K56 来最小化基因组不稳定性，从而调节复制寿命。
