Investigating site-selection mechanisms of retroviral integration in supercoiled DNA braids

We theoretically study the integration of short viral DNA in a DNA braid made up by two entwined double-stranded DNA molecules. We show that the statistics of single integration events substantially differ in the straight and buckled, or plectonemic, phase of the braid and are more likely in the latter. We further discover that integration is most likely close to plectoneme tips, where the larger bending energy helps overcome the associated energy barrier and that successive integration events are spatio-temporally correlated, suggesting a potential mechanistic explanation of clustered integration sites in host genomes. The braid geometry we consider provides a novel experimental set-up to quantify integration in a supercoiled substrate in vitro, and to better understand the role of double-stranded DNA topology during this process.

Automated summary

In this study, it was found that the integration of short viral DNA in a DNA braid is influenced by the topology of the braid, with higher likelihood of integration in the buckled phase. The research also suggests a potential mechanistic explanation for clustered integration sites in host genomes. The experimental set-up proposed provides a novel approach to quantify integration in a supercoiled substrate in vitro and sheds light on the role of double-stranded DNA topology during this process.