1. 8-Oxo-7,8-dihydrodeoxyadenosine: The first example of a native DNA lesion that stabilizes human telomeric G-quadruplex DNA
- Author
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Wanbo Liu, Manali Aggrawal, Liang Xue, Jerry Tsai, and Hyun Joo
- Subjects
HMG-box ,Base pair ,Biophysics ,Biology ,Nucleic Acid Denaturation ,G-quadruplex ,Antiparallel (biochemistry) ,Biochemistry ,Nucleic acid thermodynamics ,chemistry.chemical_compound ,Humans ,Computer Simulation ,heterocyclic compounds ,Molecular Biology ,chemistry.chemical_classification ,DNA ligase ,DNA clamp ,Deoxyadenosines ,Sodium ,Cell Biology ,Telomere ,G-Quadruplexes ,chemistry ,Potassium ,DNA ,DNA Damage - Abstract
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.
- Published
- 2012