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首页> 外文期刊>Molecular and Cellular Biology >Sites of Acetylation on Newly Synthesized Histone H4 Are Required for Chromatin Assembly and DNA Damage Response Signaling
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Sites of Acetylation on Newly Synthesized Histone H4 Are Required for Chromatin Assembly and DNA Damage Response Signaling

机译：染色质组装和DNA损伤反应信号需要新合成的组蛋白H4上的乙酰化位点

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The best-characterized acetylation of newly synthesized histone H4 is the diacetylation of the NH2-terminal tail on lysines 5 and 12. Despite its evolutionary conservation, this pattern of modification has not been shown to be essential for either viability or chromatin assembly in any model organism. We demonstrate that mutations in histone H4 lysines 5 and 12 in yeast confer hypersensitivity to replication stress and DNA-damaging agents when combined with mutations in histone H4 lysine 91, which has also been found to be a site of acetylation on soluble histone H4. In addition, these mutations confer a dramatic decrease in cell viability when combined with mutations in histone H3 lysine 56. We also show that mutation of the sites of acetylation on newly synthesized histone H4 results in defects in the reassembly of chromatin structure that accompanies the repair of HO-mediated double-strand breaks. This defect is not due to a decrease in the level of histone H3 lysine 56 acetylation. Intriguingly, mutations that alter the sites of newly synthesized histone H4 acetylation display a marked decrease in levels of phosphorylated H2A (γ-H2AX) in chromatin surrounding the double-strand break. These results indicate that the sites of acetylation on newly synthesized histones H3 and H4 can function in nonoverlapping ways that are required for chromatin assembly, viability, and DNA damage response signaling.
机译：新合成的组蛋白H4表征最充分的乙酰化是赖氨酸5和12上NH 2 末端尾巴的二乙酰化。尽管有进化上的保守性，但这种修饰方式尚未证明对在任何模型生物中的生存力或染色质组装。我们证明，与组蛋白H4赖氨酸91的突变相结合时，酵母中组蛋白H4赖氨酸5和12中的突变赋予复制应激和DNA破坏剂超敏性，后者也被发现是可溶性组蛋白H4上的乙酰化位点。此外，与组蛋白H3赖氨酸56中的突变结合时，这些突变使细胞活力急剧下降。我们还表明，新合成的组蛋白H4上乙酰化位点的突变会导致染色质结构重组伴随修复而出现缺陷HO介导的双链断裂。该缺陷不是由于组蛋白H3赖氨酸56乙酰化水平的降低。有趣的是，改变新合成的组蛋白H4乙酰化位点的突变在双链断裂周围的染色质中显示出磷酸化H2A（γ-H2AX）的水平显着降低。这些结果表明，新合成的组蛋白H3和H4上的乙酰化位点可以以不重叠的方式发挥功能，这是染色质组装，生存力和DNA损伤反应信号传递所必需的。

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