Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells
Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells
复制标题
DOI：
10.1038/emboj.2009.119
复制
发表时间：
2009-07-08
期刊：
影响因子：
11.4
通讯作者：
Jackson, Stephen P.
中科院分区：
文献类型：
--
作者：
Tjeertes, Jorrit V.;Miller, Kyle M.;Jackson, Stephen P.
受损DNA的识别和修复发生在染色质的背景下。组蛋白是染色质的关键蛋白质组分，其翻译后修饰控制着染色质的多种功能。在这里，我们报告了我们的发现，从一个大规模的屏幕DNA损伤响应组蛋白修饰在人类细胞。我们已经确定了特定的磷酸化和乙酰化组蛋白H3减少DNA损伤的反应。值得注意的是，我们发现DNA损伤诱导的H3 S10 p，H3 S28 p和H3.3S31p的变化是细胞周期重新定位的结果，而不是DNA损伤本身。相反，H3 K9 Ac和H3 K56 Ac，一种以前在人类细胞中未被表征的标记，在响应DNA损伤时迅速且可逆地减少。最后，我们表明，组蛋白乙酰转移酶GCN 5/KAT 2A乙酰化H3 K56在体外和体内。总的来说，我们的数据表明，尽管大多数组蛋白修饰在遗传毒性应激后没有明显变化，但H3 K9 Ac和H3 K56 Ac在人类细胞中响应DNA损伤而减少。The EMBO Journal（2009）28，1878-1889. doi：10.1038/doj.2009.119; 2009年4月30日在线发布
Recognition and repair of damaged DNA occurs within the context of chromatin. The key protein components of chromatin are histones, whose post-translational modifications control diverse chromatin functions. Here, we report our findings from a large-scale screen for DNA-damage-responsive histone modifications in human cells. We have identified specific phosphorylations and acetylations on histone H3 that decrease in response to DNA damage. Significantly, we find that DNA-damage-induced changes in H3S10p, H3S28p and H3.3S31p are a consequence of cell-cycle re-positioning rather than DNA damage per se. In contrast, H3K9Ac and H3K56Ac, a mark previously uncharacterized in human cells, are rapidly and reversibly reduced in response to DNA damage. Finally, we show that the histone acetyl-transferase GCN5/KAT2A acetylates H3K56 in vitro and in vivo. Collectively, our data indicate that though most histone modifications do not change appreciably after genotoxic stress, H3K9Ac and H3K56Ac are reduced in response to DNA damage in human cells. The EMBO Journal (2009) 28, 1878-1889. doi:10.1038/emboj.2009.119; Published online 30 April 2009