Influence of DNA Mispairing and Abasic Sites on Duplex Dynamics: A Temperature-Jump Infrared Spectroscopy Study

The dynamics of double-stranded DNA (dsDNA) are central to its biological role as a repository of genetic information. However, under physiological conditions DNA is subject to base mispairing and the formation of abasic sites through processes such as depurination. Such site-specific changes to the established Watson-Crick (WC) architecture would be expected to influence duplex dynamics and so affect key processes including protein binding. Here, we apply temperature-jump infrared spectroscopy to interrogate the relative impact of base pair mismatches and abasic sites on the structural dynamics of a 21-base pair (bp) dsDNA oligomer. The inclusion of an abasic site in the center of the strand leads to destabilization that is manifest as <1 μs time scale disruption of the nearby bases that is not present in fully WC-base paired sequences. Comparing this behavior with sequences featuring mismatches of different sizes shows that a single-bp mismatch causes minimal destabilization, whereas a triple base mismatch results in dynamics that closely mimic those resulting from the presence of an abasic site.