Effect of 1-methyladenine on double-helical DNA structures

• Published in: FEBS letters Vol. 582; no. 11; pp. 1629 - 1633
• Main Authors: Yang, Hao, Zhan, Yingqian, Fenn, Dickson, Chi, Lai Man, Lam, Sik Lok
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 14.05.2008
• Subjects: 1-methyladenine; 1-Methylation; 2,2-dimethyl-2-silapentane-5-sulfonic acid; Adenine; Adenine - analogs & derivatives; Adenine - chemistry; Base Pairing; Base Sequence; correlation spectroscopy; COSY; DNA; DNA - chemistry; DNA Methylation; double-quantum-filtered; double-stranded DNA; DQF; dsDNA; DSS; heteronuclear single quantum coherence spectroscopy; Hoogsteen base pair; HSQC; Hydrogen Bonding; m1A; m6A; N6-methyladenine; NMR; NOE; NOESY; nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; nuclear Overhauser effect; nuclear Overhauser effect spectroscopy; Nucleic Acid Conformation; one-dimensional; PAGE; polyacrylamide gel electrophoresis; single-stranded DNA; ssDNA; TOCSY; total correlation spectroscopy; two-dimensional; water suppression by gradient-tailored excitation; WATERGATE; 1-Methylation; NOE; DSS; Hoogsteen base pair; Adenine; PAGE; TOCSY; COSY; NMR; 2D; 1D; DNA; DQF; m6A; NOESY; m1A; HSQC; dsDNA; ssDNA; WATERGATE
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2008.04.013

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.