DNA duplex stabilization by neighboring elements through nonlocal interactions

The stability of DNA duplexes is primarily governed by base pairing interactions between complementary strands and stacking interactions with flanking or adjacent regions. For example, dangling bases can further stabilize a duplex by stacking with the terminal base pair. Here, we present a novel case where neighboring elements stabilize a duplex through nonlocal interactions. Using single-molecule FRET, we measured the effects of neighboring elements on the association (on) and dissociation (off) rates of a DNA oligo binding to its complementary strand. Our results showed that these rates vary significantly with different neighboring elements. Notably, we found that a remote DNA flank, which does not participate in base stacking, decreases both on- and off-rates, suggesting it stabilizes the duplex while hindering its formation. We propose a model in which DNA flanks suppress base pair melting by exerting ~1 pN of tension on a single-stranded gap.