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氧化损伤对人类端粒G-四重体的影响
Stasė Bielskutė1, Janez Plavec1,2,3, Peter Podbevšek1,2
1Slovenian NMR Center , National Institute of Chemistry , Hajdrihova 19 , SI-1000 Ljubljana , Slovenia.
Journal of the American Chemical Society
|January 19, 2019
概括
反应性氧物种 (ROS) 的氧化损伤可以改变DNA结构. 这项研究表明,8-oxo-7,8-dihydroguanine (oxoG) 可以破坏端粒中的G-四重复形成,影响细胞衰老.
科学领域:
- 生物化学
- 分子生物学
- 遗传学
背景情况:
- 端粒磨损与细胞衰老和反应性氧物种 (ROS) 有关.
- 对DNA的氧化损伤,特别是关氨酸,是常见的,但其结构后果尚未完全理解.
- 端粒中的G四重复结构在基因组稳定性中起着至关重要的作用.
研究的目的:
- 研究氧化损伤,特别是8-oxo-7,8-dihydroguanine (oxoG) 对人类端粒DNA (hTel) 的G-四重复形成能力的影响.
- 了解G替代如何影响DNA二级/三级结构和G-四稳定性.
- 在hTel G-四重复结构中评估oxoG的构造偏好.
主要方法:
- 在hTel寡核酸中系统地用oxoG替代guanine.
- 在修改的hTel序列中评估G-四重复形成和稳定性.
- 通过oxoG结合引起的结构重组和形状变化的分析.
主要成果:
- 大多数oxoG替代导致G-四重复结构的损失,原因是减少了结合.
- 在hTel序列中的某些位置可以容忍oxoG替代,保持一些结构完整性.
- G对同位体结构的偏好引发了不同的结构反应,包括主要的结构变化.
- 由此产生的G-四重复结构在生理温度下保持稳定.
结论:
- 氧G的结合显著影响hTel G四重复的形成和稳定性.
- oxoG的位置和糖体构造影响了结构结果.
- 这些修改后的G-四重复结构虽然有变化,但它们是稳定的,并且可能对高阶端粒结构和诸如衰老等细胞过程产生有害影响.
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