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首页> 外文期刊>Biochemistry >The Fifth Domain in the G-Quadruplex-Forming Sequence of the Human NEIL3 Promoter Locks DNA Folding in Response to Oxidative Damage
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The Fifth Domain in the G-Quadruplex-Forming Sequence of the Human NEIL3 Promoter Locks DNA Folding in Response to Oxidative Damage

机译：人类 neil3的形成序列中的第五个结构序列在响应于氧化损伤时锁定DNA折叠

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摘要

DNA oxidation is an inevitable and usually detrimental process, but the cell is capable of reversing this state because the cell possesses a highly developed set of DNA repair machineries, including the DNA glycosylase NEIL3 that is encoded by the NEIL3 gene. In this work, the G-rich promoter region of the human NEIL3 gene was shown to fold into a dynamic G-quadruplex (G4) structure under nearly physiological conditions using spectroscopic techniques (e.g., nuclear magnetic resonance, circular dichroism, fluorescence, and ultraviolet–visible) and DNA polymerase stop assays. The presence of 8-oxo-7,8-dihydroguanine (OG) modified the properties of the NEIL3 G4 and entailed the recruitment of the fifth domain to function as a “spare tire”, in which an undamaged fifth G-track is swapped for the damaged section of the G4. The polymerase stop assay findings also revealed that owing to its dynamic polymorphism, the NEIL3 G4 is more readily bypassed by DNA polymerase I (Klenow fragment) than well-known oncogene G4s are. This study identifies the NEIL3 promoter possessing a G-rich element that can adopt a G4 fold, and when OG is incorporated, the sequence can lock into a more stable G4 fold via recruitment of the fifth track of Gs.
机译：DNA氧化是不可避免的和通常有害的过程，但是该细胞能够逆转这种状态，因为该细胞具有高度发达的对DNA修复机械组，包括由 Neil3基因编码的DNA糖基酶Neil3。在这项工作中，显示人 Neil3基因的富富型启动子区域在几乎使用光谱技术（例如，核磁共振，圆形二色性，荧光和紫外线可见）和DNA聚合酶止动测定。 8-氧代-7,8-二氢胍（OG）的存在改性了 Neil3 G4的性质，并因此需要将第五个域招募作为“备用轮胎”，其中一个未损坏的第五G-Track换装为G4的受损部分。聚合酶止动测定结果还显示出由于其动态多态性，通过比众所周知的癌基因G4s更容易绕过DNA聚合酶I（Klenow片段）。该研究鉴定了具有可以采用G4折叠的G-富含G型元素的 Neil3启动子，并且当og被掺入时，序列可以通过募集GS的第五轨迹锁定更稳定的G4折叠。

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