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8-Oxoguanine Forms Quartets with a Large Central Cavity

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Oxidation of a guanine nucleotide in DNA yields an 8-oxoguanine nucleotide (oxoG) and is a mutagenic event in the genome. Due to different arrangements of hydrogen-bond donors and acceptors, oxoG… Click to show full abstract

Oxidation of a guanine nucleotide in DNA yields an 8-oxoguanine nucleotide (oxoG) and is a mutagenic event in the genome. Due to different arrangements of hydrogen-bond donors and acceptors, oxoG can affect the secondary structure of nucleic acids. We have investigated base pairing preferences of oxoG in the core of a tetrahelical G-quadruplex structure, adopted by analogues of d(TG4T). Using spectroscopic methods, we have shown that G-quartets can be fully substituted with oxoG nucleobases to form an oxoG-quartet with a revamped hydrogen-bonding scheme. While an oxoG-quartet can be incorporated into the G-quadruplex core without distorting the phosphodiester backbone, larger dimensions of the central cavity change the cation localization and exchange properties.

Keywords: cavity; central cavity; oxoguanine forms; quartets large; forms quartets; large central

Journal Title: Biochemistry
Year Published: 2022

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