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An abasic site is the most common lesion in DNA. It is also an intermediate product formed during base excision repair. Previously, we demonstrated that strand slippage can occur in primer-template model systems containing any kind of natural templating bases, suggesting deletion and expansion errors are possible in any kind of sequences during DNA replication. In this study, nuclear magnetic resonance spectroscopic investigations have been performed to study the intrinsic effect of a templating abasic residue on strand slippage in primer-template models. A DNA hairpin model system containing an abasic site and a 5'-overhang region was used to mimic the situation that a dNTP has just been incorporated opposite the abasic site. Our results show that, after dNTP incorporation, strand slippage occurs regardless of the type of terminal base pair formed. Compared to natural templating bases, abasic sites possess a higher slippage propensity, implicating a higher chance of expansion or deletion errors during DNA replication.

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.

A proton chemical shift prediction method has been developed for double helical DNAs containing A.A mismatches. This method makes use of the chemical shift prediction scheme for normal B-DNA duplexes developed by Altona and co-workers and a set of A.A mismatch triplet chemical shift values and corrections factors extracted from reference sequences. The triplet values are used for predicting chemical shifts of A.A mismatches whereas the normal B-DNA chemical shifts and correction factors are used for the flanking residues of A.A mismatches. Both 5'- and 3'-correction factors have been determined from the chemical shift differences upon replacing the A.A mismatch in a duplex with an A.T base pair. Based on 560 sets of predicted and experimental chemical shifts, the overall prediction accuracy for various types of protons has been determined to be 0.07 ppm with an excellent correlation coefficient of 0.9996.