ja5b10172_si_001.pdf (2.71 MB)
N7 Methylation Alters Hydrogen-Bonding Patterns of Guanine in Duplex DNA
journal contribution
posted on 2015-11-11, 00:00 authored by Yi Kou, Myong-Chul Koag, Seongmin LeeN7-Alkyl-2′-deoxyguanosines
are major adducts in DNA that
are generated by various alkylating mutagens and drugs. However, the
effect of the N7 alkylation on the hydrogen-bonding patterns of the
guanine remains poorly understood. We prepared N7-methyl-2′-deoxyguanosine
(N7mdG)-containing DNA using a transition-state destabilization strategy,
developed a novel polβ-host–guest complex system, and
determined eight crystal structures of N7mdG or dG paired with dC,
dT, dG, and dA. The structures of N7mdG:dC and N7mdG:dG are very similar
to those of dG:dC and dG:dG, respectively, indicating the involvement
of the keto tautomeric form of N7mdG in the base pairings with dC
and dG. On the other hand, the structure of N7mdG:dT shows that the
mispair forms three hydrogen bonds and adopts a Watson–Crick-like
geometry rather than a wobble geometry, suggesting that the enol tautomeric
form of N7mdG involves in its base pairing with dT. In addition, N7mdG:dA
adopts a novel shifted anti:syn base
pair presumably via the enol tautomeric form of N7mdG. The polβ-host–guest
complex structures reveal that guanine-N7 methylation changes the
hydrogen-bonding patterns of the guanine when paired with dT or dA
and suggest that N7 alkylation may alter the base pairing patterns
of guanine by promoting the formation of the rare enol tautomeric
form of guanine.