Detection and quantification of counterion-mediated homologous recognition in double-stranded DNA

Stretches of double-stranded DNA sharing the same sequence can recognise each other in cells. This phenomenon, known as homologous recognition, is essential for DNA recombination and repair. Yet, its mechanism remains debated, with purely physical duplex duplex interactions being proposed as a contributing factor. Here, we use a simple DNA nanodevice to precisely quantify homology-driven interactions. We find that homology enhances the DNA-DNA affinity induced by physiological divalent cations and measure the homology-driven recognition free energy as ~−0.02 kT per base pair. This affinity substantially enhances coalignment of homologous DNA in the confined geometry of the nanodevice, and could be significant in concentrated biological environments. We introduce a quantitative electrostatic theory that attributes the observed recognition to coherent charge distributions on the surface of homologous duplexes. Our findings provide compelling evidence in support of a poorly understood class of non-canonical, sequence-specific interactions between intact double-stranded DNA, which may bear biological rel- evance for homologous recognition.