8-Oxo-7,8-dihydrodeoxyadenosine: The first example of a native DNA lesion that stabilizes human telomeric G-quadruplex DNA

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• 作者：Manali Aggrawal ; Hyun Joo ; Wanbo Liu ; Jerry Tsai ; Liang Xue ; ^{lxue@pacific.edu}
• 关键词：DNA lesions ; G-quadruplex DNA ; Thermal denaturation ; DNA conformations
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：18 May, 2012
• 卷：421
• 期：4
• 页码：671-677
• 文件大小：800 K

摘要

Native DNA lesions in general destabilize DNA secondary structures such as duplex and G-quadruplex because they disrupt optimized interactions in DNA defined by nature. In this paper, we report the first example of a native DNA lesion (8-oxo-7,8-dihydrodeoxyadenosine, OxodA) that stabilizes human telomeric G-quadruplex DNA. CD thermal denaturation studies explicitly displayed increased melting temperatures of telomeric G-quadruplex DNAs that contain OxodA(s) in different DNA loops, suggesting enhanced thermal stability. Conformation studies of G-quadruplex DNAs containing OxodA(s) in the loops using CD and native PAGE revealed that they adopt a similar antiparallel conformation in Na⁺ but have much more versatile conformations in K⁺. According to computational calculations, the observed stabilization may result from the tight binding of K⁺ into the pocket formed by the O8 of OxodA and its loop. The study reported here may provide better understanding of the effect of DNA lesions on G-quadruplex stability and conformation.