氧化损伤细调G-四重复结构在人类基因促进器中
Yu Wang1, Yingying Wang1, Rongshuang Cheng1
1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research, China Pharmaceutical University, Nanjing, China.
Angewandte Chemie (International ed. in English)
|March 7, 2026
概括
氧化损伤会产生8-oxoguanine (O8G),改变基因表达. 这项研究揭示了O8G稳定了NEIL3 G四重复结构,影响了基因调节和细胞对氧化应激反应.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 结构生物学 结构生物学
背景情况:
- 氧化损伤,特别是关氨酸转化为8-oxoguanine (O8G),与基因表达变化和基因组不稳定性有关.
- 通过O8G影响这些过程的精确分子机制尚未完全理解.
研究的目的:
- 研究O8G修饰对NEIL3基因促进体G-四复合体 (NEIL3-G4s) 的结构影响.
- 阐明O8G诱导的结构变化在表观遗传调节和细胞对氧化应激反应中的作用.
主要方法:
- 核磁共振 (NMR) 光谱法用于确定原生和O8G修饰的NEIL3-G4s的溶液结构.
- 功能性试验评估NEIL3-G4s在氧化应激下对DNA聚合酶活性和基因表达的影响.
主要成果:
- 尼尔3促进子序列形成多态平行和混合G-四重复结构 (NEIL3-G4s).
- 特定站点的O8G修改显著减少了NEIL3-G4多态,稳定了特定的拓,如 (3+1) 混合-1 G4.
- 一次G-到-O8G的替代引发了结构性转变,证明了O8G对G4介导的表观遗传调节的深刻影响.
- 原生和O8G修饰的NEIL3-G4都抑制了DNA聚合酶的活性.
- 在氧化应激下,NEIL3-G4形成与增加的NEIL3基因表达相关.
结论:
- O8G修改会在NEIL3-G4s中诱导特定的结构重组,影响它们的功能.
- NEIL3-G4s作为氧化损伤的传感器和NEIL3基因上调调节的分子开关.
- 由O8G诱导的G4结构可塑性对于细胞对氧化应激反应和基因表达调节至关重要.
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