The structural stability of DNA plays a crucial role in the success of life. This stability arises not only from the base-pairing interactions that form the double-stranded structure of DNA, but also from base-stacking interactions that drive DNA to adopt its characteristic helical conformation. These base-stacking interactions have long been of great interest to the scientific community. However, over the past two and a half decades, various assays designed to measure these interactions have produced results that lack clear consensus. This discrepancy has prompted us to question the mere assumption that base-stacking interaction strengths are dictated solely by the two nucleotides directly involved. Our recent data reveal that the influence of nearest-neighbor nucleotides is non-trivial, significant, and in some cases, alter the trends that are reported in studies. To investigate this effect, we employed a single-molecule assay based on the transient binding of two single-stranded DNA molecules along with barcoded DNA origami structures to drive high-throughput measurements, enabling us to uncover how the first nearest neighbors of a given dinucleotide modulate base-stacking interactions.
Gupta et al. (Sun,) studied this question.
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