title: 8-Oxo-7,8-dihydrodeoxyadenosine: the first example of a native DNA lesion that stabilizes human telomeric G-quadruplex DNA.
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.
authors.affiliation: Department of Chemistry, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Manali
authors.initials: M
authors.lastname: Aggrawal
authors.forename: Hyun
authors.initials: H
authors.lastname: Joo
authors.forename: Wanbo
authors.initials: W
authors.lastname: Liu
authors.forename: Jerry
authors.initials: J
authors.lastname: Tsai
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
mesh_terms: D003198:Computer Simulation; D004249:DNA Damage; D003839:Deoxyadenosines / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D009691:Nucleic Acid Denaturation; D011188:Potassium; D012964:Sodium; D016615:Telomere / Q000737:chemistry*
chemical_list: D003839:Deoxyadenosines; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D012964:Sodium; D011188:Potassium