在Duplex-G-Quadruplex-Duplex上下文中,DNA损伤加速G-四倍折叠
Aaron M Fleming1, Brandon Leonel Guerra Castañaza Jenkins1, Bethany A Buck1
1Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
Journal of the American Chemical Society
|April 11, 2024
概括
DNA损伤显著影响潜在的G四重复序列 (PQS) 的折叠,影响基因调节. DNA 断裂加速了 PQS 折叠, 影响了细胞的复制和修复过程.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 潜在的G四重复序列 (PQS) 形成了对基因调节至关重要的非正规DNA结构.
- 对PQS折叠动态的DNA损伤的影响尚不清楚.
- PQS折叠的基因组DNA约束是由双重-G-四重-双重 (DGD) 支架模拟的.
研究的目的:
- 研究DNA基损伤和链断裂对PQS折叠运动的影响.
- 使用VEGF促进子序列分析DGD支架中的PQS折叠.
- 确定损伤对细胞时间表相关的PQS折叠的影响.
主要方法:
- 循环二重化 (CD) 光谱检测折叠动力学.
- 1D质子核磁共振 (1H NMR) 用于结构分析.
- 使用双重-G-四重-双重 (DGD) 支架用于VEGF促进体序列.
主要成果:
- 根据DNA损伤类型和位置,折叠半衰期从2秒到12分钟不等.
- 一个单一的线程断裂在G运行加速折叠>150倍.
- 2+离子和APE1蛋白促进了PQS折叠.
- CD和NMR证实了G4的形成和受损的折叠.
结论:
- DNA损伤,特别是链断裂,显著改变了PQS折叠动力学.
- VEGF促进体PQS折叠对DNA损伤的类型和位置非常敏感.
- 测量的折叠半衰期与DNA复制,转录和修复过程有关.
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