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Effect of Pressure on Thermal Stability of G-Quadruplex DNA and Double-Stranded DNA Structures

机译:压力对G-四链体DNA和双链DNA结构热稳定性的影响

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摘要

Pressure is a thermodynamic parameter that can induce structural changes in biomolecules due to a volumetric decrease. Although most proteins are denatured by pressure over 100 MPa because they have the large cavities inside their structures, the double-stranded structure of DNA is stabilized or destabilized only marginally depending on the sequence and salt conditions. The thermal stability of the G-quadruplex DNA structure, an important non-canonical structure that likely impacts gene expression in cells, remarkably decreases with increasing pressure. Volumetric analysis revealed that human telomeric DNA changed by more than 50 cm~3 mol~(-1) during the transition from a random coil to a quadruplex form. This value is approximately ten times larger than that for duplex DNA under similar conditions. The volumetric analysis also suggested that the formation of G-quadruplex DNA involves significant hydration changes. The presence of a cosolute such as poly(ethylene glycol) largely repressed the pressure effect on the stability of G-quadruplex due to alteration in stabilities of the interactions with hydrating water. This review discusses the importance of local perturbations of pressure on DNA structures involved in regulation of gene expression and highlights the potential for application of high-pressure chemistry in nucleic acid-based nanotechnology.
机译:压力是一种热力学参数,由于体积减小,可以引起生物分子的结构变化。尽管大多数蛋白质由于其结构内部都具有大空腔而在超过100 MPa的压力下被变性,但DNA的双链结构仅在一定程度上取决于序列和盐条件而稳定或不稳定。 G-四链体DNA结构(可能影响细胞中基因表达的重要非规范结构)的热稳定性会随着压力的增加而显着降低。体积分析表明,人类端粒DNA在从无规卷曲转变为四重体的过程中变化超过50 cm〜3 mol〜(-1)。在类似条件下,该值约为双链DNA的十倍。体积分析还表明,G-四链体DNA的形成涉及显着的水合变化。诸如聚(乙二醇)之类的溶质的存在由于与水合水的相互作用的稳定性改变而大大抑制了对G-四链体的稳定性的压力作用。这篇综述讨论了局部微调压力对参与基因表达调控的DNA结构的重要性,并强调了高压化学在基于核酸的纳米技术中的应用潜力。

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