Regulation of histone H3 lysine 56 acetylation in Schizosaccharomyces pombe
Regulation of histone H3 lysine 56 acetylation in Schizosaccharomyces pombe
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DOI：
10.1074/jbc.m701197200
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发表时间：
2007-05-18
影响因子：
4.8
通讯作者：
Arcangioli, Benoit
中科院分区：
文献类型：
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作者：
Xhemalce, Blerta;Miller, Kyle M.;Arcangioli, Benoit
在酿酒酵母中，组蛋白H3球状结构域中赖氨酸56(Lys-56)的乙酰化在响应干扰DNA复制的遗传毒物方面起着重要作用。然而，在其他真核生物中，这种修饰的调节和生物学功能并不清楚。在这里，我们发现裂殖酵母中的Lys-56乙酰化发生在通过S相的过程中，通常在G2期被移除。在复制过程中导致DNA双链断裂的遗传毒性物质会导致组蛋白H3Lys-56的脱乙酰化延迟。此外，不能乙酰化Lys-56的突变细胞对阻止DNA复制的遗传毒性物质非常敏感。此外，我们还发现Spbc342.06cp是一个以前未被描述的开放阅读框架，它编码了酿酒酵母Rtt109的功能同源物，并且该蛋白在体外和体内都能乙酰化H3Lys-56。综上所述，我们的结果表明，组蛋白H3Lys-56由其组蛋白乙酰基转移酶和组蛋白去乙酰基酶调节的乙酰化及其在DNA损伤反应中的作用在两个远缘酵母模式生物中都是保守的。
In Saccharomyces cerevisiae, acetylation of lysine 56 ( Lys-56) in the globular domain of histone H3 plays an important role in response to genotoxic agents that interfere with DNA replication. However, the regulation and biological function of this modification are poorly defined in other eukaryotes. Here we show that Lys-56 acetylation in Schizosaccharomyces pombe occurs transiently during passage through S-phase and is normally removed in G2. Genotoxic agents that cause DNA double strand breaks during replication elicit a delay in deacetylation of histone H3 Lys-56. In addition, mutant cells that cannot acetylate Lys-56 are acutely sensitive to genotoxic agents that block DNA replication. Moreover, we show that Spbc342.06cp, a previously uncharacterized open reading frame, encodes the functional homolog of S. cerevisiae Rtt109, and that this protein acetylates H3 Lys-56 both in vitro and in vivo. Altogether, our results indicate that both the regulation of histone H3 Lys-56 acetylation by its histone acetyltransferase and histone deacetylase and its role in the DNA damage response are conserved among two distantly related yeast model organisms.