Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics

Ashwood, Brennan; Jones, Michael S.; Lee, Yumin; Sachleben, Joseph R.; Ferguson, Andrew L.; Tokmakoff, Andrei

doi:10.1016/j.bpj.2023.11.022

Biophysical Journal

2024

DOI: 10.1016/j.bpj.2023.11.022

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Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics

Brennan Ashwood,

Michael S. Jones,

Yumin Lee

et al.

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Cited by 2 publications

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Insights into nucleic acid helix formation from infrared spectroscopy

Schroeder

2024

Biophysical Journal

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Insights into nucleic acid helix formation from infrared spectroscopy

Schroeder

2024

Biophysical Journal

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Transient states during the annealing of mismatched and bulged oligonucleotides

Todisco,

Ding,

Szostak

2024

Nucleic Acids Research

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Oligonucleotide hybridization is crucial in various biological, prebiotic and nanotechnological processes, including gene regulation, non-enzymatic primer extension and DNA nanodevice assembly. Although extensive research has focused on the thermodynamics and kinetics of nucleic acid hybridization, the behavior of complex mixtures and the outcome of competition for target binding remain less well understood. In this study, we investigate the impact of mismatches and bulges in a 12 bp DNA or RNA duplex on its association (kon) and dissociation (koff) kinetics. We find that such defects have relatively small effects on the association kinetics, while the dissociation kinetics vary in a position-dependent manner by up to 6 orders of magnitude. Building upon this observation, we explored a competition scenario involving multiple oligonucleotides, and observed a transient low specificity of probe hybridization to fully versus partially complementary targets in solution. We characterize these long-lived metastable states and their evolution toward equilibrium, and show that sufficiently long-lived mis-paired duplexes can serve as substrates for prebiotically relevant chemical copying reactions. Our results suggest that transient low accuracy states may spontaneously emerge within all complex nucleic acid systems comprising a large enough number of competing strands, with potential repercussions for gene regulation in the realm of modern biology and the prebiotic preservation of genetic information.

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Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics

Cited by 2 publications

References 88 publications

Insights into nucleic acid helix formation from infrared spectroscopy

Insights into nucleic acid helix formation from infrared spectroscopy

Transient states during the annealing of mismatched and bulged oligonucleotides

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