Influence of DNA mispairing and abasic sites on duplex dynamics : a temperature-jump infrared spectroscopy study

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Hunt, Neil T. and Kendall-Price, Sophie E. T. and Phelps, Ryan and Greetham, Gregory M. and Burley, Glenn A. (2026) Influence of DNA mispairing and abasic sites on duplex dynamics : a temperature-jump infrared spectroscopy study. Journal of Physical Chemistry Letters, 17 (25). pp. 7111-7119. ISSN 1948-7185 (https://doi.org/10.1021/acs.jpclett.6c00991)

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Abstract

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.

ORCID iDs

Hunt, Neil T. ORCID logoORCID: https://orcid.org/0000-0001-7400-5152, Kendall-Price, Sophie E. T., Phelps, Ryan, Greetham, Gregory M. and Burley, Glenn A. ORCID logoORCID: https://orcid.org/0000-0002-4896-113X;
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