组蛋白 H3 赖氨酸 56 乙酰化增强 AP 内切核酸酶 1 介导的核小体核心颗粒中 AP 位点的修复。
Histone H3 Lysine 56 Acetylation Enhances AP Endonuclease 1-Mediated Repair of AP Sites in Nucleosome Core Particles.
机构信息
Genome Integrity and Structural Biology Laboratory , National Institute of Environmental Health Sciences , Research Triangle Park , North Carolina 27709 , United States.
出版信息
Biochemistry. 2019 Sep 3;58(35):3646-3655. doi: 10.1021/acs.biochem.9b00433. Epub 2019 Aug 16.
Deciphering factors modulating DNA repair in chromatin is of great interest because nucleosomal positioning influences mutation rates. H3K56 acetylation (Ac) is implicated in chromatin landscape regulation, impacting genomic stability, yet the effect of H3K56Ac on DNA base excision repair (BER) remains unclear. We determined whether H3K56Ac plays a role in regulating AP site incision by AP endonuclease 1 (APE1), an early step in BER. Our studies of acetylated, well-positioned nucleosome core particles (H3K56Ac-601-NCPs) demonstrate APE1 strand incision is enhanced compared with that of unacetylated WT-601-NCPs. The high-mobility group box 1 protein enhances APE1 activity in WT-601-NCPs, but this effect is not observed in H3K56Ac-601-NCPs. Therefore, our results suggest APE1 activity on NCPs can be modulated by H3K56Ac.
解析影响染色质中 DNA 修复的因素非常重要，因为核小体定位会影响突变率。H3K56 乙酰化（Ac）与染色质景观调节有关，影响基因组稳定性，但 H3K56Ac 对 DNA 碱基切除修复（BER）的影响尚不清楚。我们确定 H3K56Ac 是否在调节 AP 内切酶 1（APE1）切割 AP 位点中发挥作用，AP 内切酶 1 是 BER 的早期步骤。我们对乙酰化、定位良好的核小体核心颗粒（H3K56Ac-601-NCPs）的研究表明，与未乙酰化的 WT-601-NCPs 相比，APE1 链切割增强。高迁移率族框 1 蛋白增强 WT-601-NCPs 中 APE1 的活性，但在 H3K56Ac-601-NCPs 中未观察到这种效应。因此，我们的结果表明，H3K56Ac 可以调节 NCPs 上的 APE1 活性。
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