TY - JOUR
T1 - Dynamics of 8-Oxoguanine in DNA: Decisive Effects of Base Pairing and Nucleotide Context
AU - Ovcherenko, Sergey S
AU - Shernyukov, Andrey V
AU - Nasonov, Dmitry M
AU - Endutkin, Anton V
AU - Zharkov, Dmitry O
AU - Bagryanskaya, Elena G
N1 - Funding: This study was supported by Russian Science Foundation (21-14-00219). Partial salary support from Russian Ministry of Science and Higher Education (12103130005-8) is acknowledged.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - https://www.mendeley.com/catalogue/29550847-2d17-31f9-8119-491677197e75/
U2 - 10.1021/jacs.2c11230
DO - 10.1021/jacs.2c11230
M3 - Article
C2 - 36867834
VL - 145
SP - 5613
EP - 5617
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 10
ER -