Supercoiled DNA Minicircles under Double-strand Breaks

Understanding how supercoiled DNA releases intramolecular stress is essential for its functional realization. However, the molecular mechanism underlying the relaxation process remains insufficiently explored. Here we employed MD simulations based on the oxDNA2 model to investigate the relaxation process of a 336-base pair supercoiled minicircular DNA under double-strand breaks with two fixed endpoints. Our simulations show that the conformational changes in the DNA occur continuously, with intramolecular stress release happening abruptly only when the DNA chain traverses the breakage site. The relaxation process is influenced not only by the separation distance between the fixed ends but also their angle. Importantly, we observe an inhibitory effect on the relaxation characterized by small angles, where short terminal loops impede DNA conformational adjustments, preserving the supercoiled structure. These findings elucidate the intricate interplay between DNA conformational change, DNA motion and intramolecular stress release, shedding light on the mechanisms governing the relaxation of supercoiled DNA at the molecular level.