Effect of 1-methyladenine on double-helical DNA structures

Abstract 

Methylation at the N1 site of adenine leads to the formation of cytotoxic 1-methyladenine (m1A). Since the N1 site of adenine is involved in the hydrogen bonding of T·A and A·T Watson–Crick base pairs, it is expected that the pairing interactions will be disrupted upon 1-methylation. In this study, high-resolution NMR investigations were performed to determine the effect of m1A on double-helical DNA structures. Interestingly, instead of disrupting hydrogen bonding, we found that 1-methylation altered the T·A Watson–Crick base pair to T(anti)·m1A(syn) Hoogsteen base pair, providing insights into the observed differences in AlkB-repair efficiency between dsDNA and ssDNA.

Abbreviations: m1A, 1-methyladenine, m6A, N6-methyladenine, NMR, nuclear magnetic resonance, dsDNA, double-stranded DNA, ssDNA, single-stranded DNA, PAGE, polyacrylamide gel electrophoresis, 1D, one-dimensional, 2D, two-dimensional, NOE, nuclear Overhauser effect, NOESY, nuclear Overhauser effect spectroscopy, TOCSY, total correlation spectroscopy, DQF, double-quantum-filtered, COSY, correlation spectroscopy, HSQC, heteronuclear single quantum coherence spectroscopy, DSS, 2,2-dimethyl-2-silapentane-5-sulfonic acid, WATERGATE, water suppression by gradient-tailored excitation

Keywords: NMR, DNA, 1-Methylation, Adenine, Hoogsteen base pair