Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis
Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis
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DOI：
10.1073/pnas.0601676103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Allis, CD
中科院分区：
文献类型：
--
作者：
Recht, J;Tsubota, T;Allis, CD
组蛋白乙酰化会影响许多核过程，包括转录，染色质组装和DNA损伤修复。芽孢杆菌H3赖氨酸56（H3 K56AC）在萌芽酵母中的乙酰化发生在有丝分裂的S期，并且在DNA损伤修复过程中持续存在。在这里，我们表明H3 K56Ac在前阶段也存在，并且在裂变酵母中保守。此外，在没有组蛋白伴侣ASF1的情况下，未观察到H3 K56AC修饰。 ASF1三角洲和H3 K56R突变体对DNA损害剂的敏感性相似。 ASF1的突变分析表明，DNA损伤敏感性与（i）降低H3 K56AC和（ii）与组蛋白结合有关的区域。相反，对DNA损伤具有抗性的多个ASF1突变体显示了K56AC的WT水平。这些数据表明，H3 K56乙酰化的维持是ASF1对酵母基因组稳定性的主要贡献。
Histone acetylation affects many nuclear processes including transcription, chromatin assembly, and DNA damage repair. Acetylation of histone H3 lysine 56 (H3 K56ac) in budding yeast occurs during mitotic S phase and persists during DNA damage repair. Here, we show that H3 K56ac is also present during premeiotic S phase and is conserved in fission yeast. Furthermore, the H3 K56ac modification is not observed in the absence of the histone chaperone Asf1. asf1 Delta and H3 K56R mutants exhibit similar sensitivity to DNA damaging agents. Mutational analysis of Asf1 demonstrates that DNA damage sensitivity correlates with (i) decreased levels of H3 K56ac and (ii) a region implicated in histone binding. In contrast, multiple asf1 mutants that are resistant to DNA damage display WT levels of K56ac. These data suggest that maintenance of H3 K56 acetylation is a primary contribution of Asf1 to genome stability in yeast.