Abstract: 8-Oxo-7,8-dihydroguanine (oxoG), an abundant DNA lesion, can mispair with adenine and induce mutations. To prevent this, cells possess DNA repair glycosylases that excise either oxoG from oxoG:C pairs (bacterial Fpg, human OGG1) or A from oxoG:A mispairs (bacterial MutY, human MUTYH). Early lesion recognition steps remain murky and may include enforced base pair opening or capture of a spontaneously opened pair. We adapted the CLEANEX-PM NMR protocol to detect DNA imino proton exchange and analyzed the dynamics of oxoG:C, oxoG:A, and their undamaged counterparts in nucleotide contexts with different stacking energy. Even in a poorly stacking context, the oxoG:C pair did not open easier than G:C, arguing against extrahelical base capture by Fpg/OGG1. On the contrary, oxoG opposite A significantly populated the extrahelical state, which may assist recognition by MutY/MUTYH.

Cite: Ovcherenko S.S. , Shernyukov A.V. , Nasonov D.M. , Endutkin A.V. , Zharkov D.O. , Bagryanskaya E.G.
Dynamics of 8-oxoguanine in DNA: Decisive effects of base pairing and nucleotide context.
Journal of the American Chemical Society. 2023. V.145. N10. P.5591-5988. DOI: 10.1021/jacs.2c11230 WOS Scopus РИНЦ

Dates:

Submitted:	Oct 24, 2022
Published online:	Mar 2, 2023

Identifiers:

Web of science	WOS:000943330600001
Scopus	2-s2.0-85149386454
Elibrary	60881080
OpenAlex	W4322769319

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