人类NEIL3基因表达通过表观基因类似的氧化DNA修饰进行调节
Aaron M Fleming1, Judy Zhu1, Shereen A Howpay Manage1
1Department of Chemistry , University of Utah , Salt Lake City , Utah 84112-0850 , United States.
Journal of the American Chemical Society
|June 27, 2019
概括
尼尔3 DNA 修复基因
科学领域:
- 基因组学
- DNA 修复
- 表观遗传学
背景情况:
- 氧化和炎症压力诱导NEIL3基因表达.
- 在压力过程中,瓜 (G) 氧化为8-oxo-7,8-dihydroguanine (OG).
- 在NEIL3中,一个富含G的促进子元素是潜在的G四重复形成序列 (PQS).
研究的目的:
- 研究NEIL3 PQS在氧化应激过程中的基因调节作用.
- 探索涉及OG形成和修复的NEIL3激活机制.
- 要确定NEIL3 PQS是否作为一个氧化回收敏感的调节元件.
主要方法:
- 使用热力学和化学分析的体外研究.
- 对DNA修复过程的研究.
- 哺乳动物基因组的生物信息分析以保存序列.
主要成果:
- 在NEIL3 PQS中的OG形成触发了OGG1的基切除修复,形成了一个基切除位点 (AP).
- 在PQS中促进G-四重复 (G4) 折叠.
- 在G4环境中,APE1很难切割AP位点,使其能够充当转录交换激活器.
结论:
- NEIL3 PQS 作为氧化还原开关,通过OG修饰调节NEIL3的表达.
- 这种机制允许细胞在氧化应激过程中对突变性DNA损伤做出反应.
- 在哺乳动物基因组中保存的NEIL3 PQS表明了这一调节途径的进化选择.
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