Recht J, Tsubota T, Tanny J C, Diaz R L, Berger J M, Zhang X, Garcia B A, Shabanowitz J, Burlingame A L, Hunt D F, Kaufman P D, Allis C D
Laboratory of Chromatin Biology, The Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6988-93. doi: 10.1073/pnas.0601676103. Epub 2006 Apr 20.
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. asf1delta 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.
组蛋白乙酰化影响许多核过程，包括转录、染色质组装和DNA损伤修复。出芽酵母中组蛋白H3赖氨酸56（H3 K56ac）的乙酰化发生在有丝分裂S期，并在DNA损伤修复过程中持续存在。在此，我们表明H3 K56ac在减数分裂前S期也存在，并且在裂殖酵母中保守。此外，在没有组蛋白伴侣Asf1的情况下未观察到H3 K56ac修饰。asf1delta和H3 K56R突变体对DNA损伤剂表现出相似的敏感性。Asf1的突变分析表明，DNA损伤敏感性与（i）H3 K56ac水平降低和（ii）与组蛋白结合相关的区域有关。相反，多个对DNA损伤有抗性的asf1突变体显示出野生型水平的K56ac。这些数据表明，维持H3 K56乙酰化是Asf1对酵母基因组稳定性的主要贡献。
