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Updated: Jul 23, 2025

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过氧化衍生的DNA添加物,6-oxo-M₁dG,是人类DNA聚合酶 η复制的强有力的阻碍者

Robyn Richie-Jannetta¹, Pradeep Pallan², Philip J Kingsley¹

¹A. B. Hancock, Jr, Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry and Pharmacology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

The Journal of biological chemistry

|July 19, 2023

概括

DNA附加物6-oxo-M1dG阻断了人类聚合酶eta (hPol η) 的复制. 结构分析显示,它阻碍了DNA合成,因为它阻止了核酸的正确定位以形成基键.

科学领域:

分子生物学分子生物学
在DNA修复和复制过程中,
结构生物学结构生物学

背景情况:

通过氧化M1dG添加物形成DNA添加物6-oxo-M1dG.
6-oxo-M1dG对人类Y-家族聚合酶乙酸酶 (hPol η) 的DNA复制的影响在很大程度上是未知的.

研究的目的:

为了研究hPol η绕过6oxo-M1dGDNA引导的能力.
阐明hPol η与6-oxo-M1dG的相互作用和绕过背后的结构机制.

主要方法:

稳定状态动力学来分析核酸插入.
液体染色学-双重质谱学用于DNA延伸产品分析.
在插入和延伸阶段使用X射线晶体学来确定hPol η-DNA复合物的结构.

主要成果:

hPol η首选插入dAMP或dGMP与6-oxo-M1dG对立,对dGMP有轻微的偏好.
使用3'-终端dGMP或dAMP跨越6-oxo-M1dG的原始剂的扩展比使用dCMP或dTMP更有效.
结构分析显示,6-oxo-M1dG与活性部位没有相互作用,而是与相邻的基堆叠在一起,并且它使3'-基组不对齐,阻断了基键的形成.

结论:

该DNA附加物6-oxo-M1dG作为一个显著阻断DNA复制的hPol η.
结构洞察力解释了6-oxo-M1dG的阻断能力,突出了它对核酸结合和延伸的干扰.

关键词:

6-oxo-M(1) dGG-M(1) 是一个可靠的化学物质.DNA 添加物添加物的 DNA.造成的DNA损伤是DNA损伤.DNA聚合酶是一种DNA聚合酶.修复DNA的修复DNA的修复 M (((1) dGG) 的意思.氧化作用的损伤.在X射线晶体学.突变发生机制突变发生机制转化合成的转化合成

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