在VEGF G-四倍体形成促进体上的氧化DNA损伤通过长贴BER修复
Adil S Hussen1, Haley L Kravitz2, Bret D Freudenthal1
1Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Environmental and molecular mutagenesis
|August 22, 2023
概括
基切除修复 (BER) 酶通过与受损的G4DNA相互作用来修改VEGF基因表达. 这项研究揭示了OGG1,APE1,Polβ和FEN1等BER因子如何协调VEGF G4促进者的修复.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 氧化性DNA损伤通过表观遗传性修饰影响基因表达.
- 基切除修复 (BER) 酶参与修复DNA损伤.
- 在VEGF促销者的G4DNA结构上BER的特定机制尚未完全理解.
研究的目的:
- 研究单个BER酶在VEGF促进体G4DNA上的活性和协调.
- 在受损的G4DNA基板上阐明BER路径的机械细节.
- 了解BER如何对VEGF基因转录调节作出贡献.
主要方法:
- 使用稳定状态前动力学测试来分析BER酶活性.
- 为了研究修复过程,采用了体外合BER试验.
- 用VEGF促进体G4DNA基质来模仿细胞条件.
主要成果:
- OGG1发起了双链VEGF促进者G4 DNA的BER.
- 由于产品释放速度较慢,APE1对G4DNA的活性降低.
- 聚β在G4DNA上进行多重插入,需要FEN1来完成长时间的BER补丁.
结论:
- 在VEGF G4促进体DNA上的BER酶活动与B型DNA不同.
- 在VEGF G4促进体修复方面,佳能短补丁BER是不够的.
- FEN1的长补丁BER活性对于完成损坏的VEGF G4促进体DNA的修复至关重要,影响转录调节.
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