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.
CITATION STYLE
Ovcherenko, S. S., Shernyukov, A. V., Nasonov, D. M., Endutkin, A. V., Zharkov, D. O., & Bagryanskaya, E. G. (2023). Dynamics of 8-Oxoguanine in DNA: Decisive Effects of Base Pairing and Nucleotide Context. Journal of the American Chemical Society, 145(10), 5613–5617. https://doi.org/10.1021/jacs.2c11230
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