Histone acetylation plays an important role in DNA replication and repair because replicating chromatin is subject to dynamic changes in its structures. However, its precise mechanism remains elusive. In this report, we describe roles of the NuA4 acetyltransferase and histone H4 acetylation in replication fork protection in the fission yeast Schizosaccharomyces pombe. Downregulation of NuA4 subunits renders cells highly sensitive to camptothecin, a compound that induces replication fork breakage. Defects in NuA4 function or mutations in histone H4 acetylation sites lead to impaired recovery of collapsed replication forks and elevated levels of Rad52 DNA repair foci, indicating the role of histone H4 acetylation in DNA replication and fork repair. We also show that Vid21 interacts with the Swi1–Swi3 replication fork protection complex and that Swi1 stabilizes Vid21 and promotes efficient histone H4 acetylation. Furthermore, our genetic analysis demonstrates that loss of Swi1 further sensitizes NuA4 and histone H4 mutant cells to replication fork breakage. Considering that Swi1 plays a critical role in replication fork protection, our results indicate that NuA4 and histone H4 acetylation promote repair of broken DNA replication forks.

中文翻译：

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NuA4乙酰转移酶和组蛋白H4乙酰化促进拓扑异构酶I中毒后的复制恢复

组蛋白乙酰化在 DNA 复制和修复中起着重要作用，因为复制染色质会发生其结构的动态变化。然而，其精确机制仍然难以捉摸。在本报告中，我们描述了 NuA4 乙酰转移酶和组蛋白 H4 乙酰化在裂变酵母粟酒裂殖酵母复制叉保护中的作用。NuA4 亚基的下调使细胞对喜树碱高度敏感，喜树碱是一种诱导复制叉断裂的化合物。NuA4 功能缺陷或组蛋白 H4 乙酰化位点突变导致折叠复制叉的恢复受损和 Rad52 DNA 修复病灶水平升高，表明组蛋白 H4 乙酰化在 DNA 复制和叉修复中的作用。我们还表明 Vid21 与 Swi1-Swi3 复制叉保护复合物相互作用，并且 Swi1 稳定 Vid21 并促进有效的组蛋白 H4 乙酰化。此外，我们的遗传分析表明，Swi1 的缺失进一步使 NuA4 和组蛋白 H4 突变细胞对复制叉断裂敏感。考虑到 Swi1 在复制叉保护中起关键作用，我们的结果表明 NuA4 和组蛋白 H4 乙酰化促进断裂 DNA 复制叉的修复。