具有氧化修饰基的NEIL3促进剂G-四重复体显示了依赖的折叠,从而阻断了聚合酶旁路
Aaron M Fleming1, Carla A Omaga1, Cynthia J Burrows1
1Department of Chemistry, University of Utah, Salt Lake City, UT, 84112-0850, USA.
Biochimie
|July 12, 2023
概括
氧化应激可以损害DNA,在NEIL3基因促进器G-四复合体内形成8-oxo-7,8-dihydro-2'-deoxyguanosine (OG). 离子影响了这种修饰的G-四重体如何影响DNA聚合酶,影响复制.
科学领域:
- 生物化学 生物化学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 氧化应激会产生破坏DNA的反应性物种,特别是在G-丰富的基因组区域,如G-四重复.
- NEIL3基因促进体含有潜在的G-四重复形成序列 (PQS),容易受到氧化损伤.
- 2 - 脱氧氨酸 (G) 的氧化产生8-oxo-7,8-dihydro-2 - 脱氧氨酸 (OG) 和更多的氧化产物,如antoins.
研究的目的:
- 研究离子 (Mg2+) 对氧化改性NEIL3 G-四重复合物 (G4) 折叠和稳定性的影响.
- 评估OG在NEIL3 G4中的存在如何影响复制DNA聚合酶停滞和延伸.
- 为了阐明OG和hydantoin修改在不同Mg2+度下对NEIL3 G4折叠的结构后果.
主要方法:
- 合成OG进入NEIL3 PQS,随后在K+和Mg2+度不同的溶液中进行G4折叠.
- 在经过修改的NEIL3 G4中评估DNA聚合酶停滞和延伸.
- 将OG和hydantoins合成NEIL3模型G4序列,以研究不同Mg2+水平的G4折叠动态.
主要成果:
- 在NEIL3 G4或OG部位的DNA聚合酶停滞或全长延伸取决于修饰的位置和Mg2+度.
- Mg2+ 影响了 NEIL3 G4 折叠,在某些情况下诱导了从反平行到平行链方向的过渡,或者没有显著的影响.
- 提出了结构模型来解释Mg2+对修改G4折叠的观察效应.
结论:
- 离子在调节氧化损伤的NEIL3 G四复合体的结构形状和稳定性方面发挥着至关重要的作用.
- 氧化修饰的位置和Mg2+度是DNA聚合酶与修饰的G4结构相互作用的关键决定因素.
- 这些发现为G丰富基因组区域内氧化DNA损伤的生物学意义及其对DNA复制忠实性的影响提供了洞察力.
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