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

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► OxodA in the loops stabilizes human telomeric G-quadruplex DNA. ► The conformations of G-quadruplex DNAs are similar in Na+ and different in K+. ► The binding of K+ with the OxodA loop pocket may account for the stabilization.