Histone H3 Lysine 14 (H3K14) Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of the Chromatin Remodeler RSC (Remodels Structure of Chromatin)
Histone H3 Lysine 14 (H3K14) Acetylation Facilitates DNA Repair in a Positioned Nucleosome by Stabilizing the Binding of the Chromatin Remodeler RSC (Remodels Structure of Chromatin)
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DOI：
10.1074/jbc.m113.540732
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发表时间：
2014-03-21
影响因子：
4.8
通讯作者：
Smerdon, Michael J.
中科院分区：
文献类型：
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作者：
Duan, Ming-Rui;Smerdon, Michael J.
背景：组蛋白H3K14乙酰化是由紫外线损伤引起的。结果：在染色质重塑复合体RSC存在下，H3K14乙酰化的核小体比未乙酰化的核小体表现出更大的CPD修复。结论：H3K14ac作为对接位点保留核小体上的RSC，促进DNA修复。意义：紫外线诱导的组蛋白乙酰化和染色质重塑之间的协调作用加速了DNA修复。组蛋白H3乙酰化是酵母在紫外线损伤下诱导的，可能在调节核小体负载基因组位点的紫外线光损伤修复中起重要作用。然而，H3乙酰化如何促进修复尚不清楚。我们在Lys-14 （H3K14ac）上生成了一个强定位的核小体，其中含有均匀乙酰化的H3，并研究了H3K14乙酰化调节修复的可能机制。我们发现H3K14ac不会改变核小体展开动力学或增强紫外线光解酶对紫外线诱导的环丁烷嘧啶二聚体的修复。然而，重要的是，与未乙酰化的核小体相比，具有H3K14ac的核小体对纯化的染色质重塑复合体RSC（重塑染色质结构）具有更高的亲和力，并且表现出更大的环丁烷嘧啶二聚体修复。我们的研究表明，通过锚定RSC， H3K14乙酰化在紫外线损伤修复过程中强定位核小体的展开中发挥重要作用。
Background: Histone H3K14 acetylation is induced by UV damage. Results: Nucleosomes with acetylated H3K14 show greater CPD repair than unacetylated nucleosomes in the presence of the chromatin remodeling complex RSC. Conclusion: H3K14ac acts as a docking site to retain RSC on nucleosomes and facilitate DNA repair. Significance: DNA repair is accelerated by an orchestrated action between UV-induced histone acetylation and chromatin remodeling.Histone H3 acetylation is induced by UV damage in yeast and may play an important role in regulating the repair of UV photolesions in nucleosome-loaded genomic loci. However, it remains elusive how H3 acetylation facilitates repair. We generated a strongly positioned nucleosome containing homogeneously acetylated H3 at Lys-14 (H3K14ac) and investigated possible mechanisms by which H3K14 acetylation modulates repair. We show that H3K14ac does not alter nucleosome unfolding dynamics or enhance the repair of UV-induced cyclobutane pyrimidine dimers by UV photolyase. Importantly, however, nucleosomes with H3K14ac have a higher affinity for purified chromatin remodeling complex RSC (Remodels the Structure of Chromatin) and show greater cyclobutane pyrimidine dimer repair compared with unacetylated nucleosomes. Our study indicates that, by anchoring RSC, H3K14 acetylation plays an important role in the unfolding of strongly positioned nucleosomes during repair of UV damage.