Two-phase dynamics of DNA supercoiling based on DNA polymer physics.

DNA supercoils are generated in genome regulation processes such as transcription and replication and provide mechanical feedback to such processes. Under tension, a DNA supercoil can present a coexistence state of plectonemic and stretched phases. Experiments have revealed the dynamic behaviors of plectonemes, e.g., diffusion, nucleation, and hopping. To represent these dynamics with conformational changes, we demonstrated first the fast dynamics on the DNA to reach torque equilibrium within the plectonemic and stretched phases, and then identified the two-phase boundaries as collective slow variables to describe the essential dynamics. According to the timescale separation demonstrated here, we developed a two-phase model on the dynamics of DNA supercoiling, which can capture physiologically relevant events across timescales of several orders of magnitudes. In this model, we systematically characterized the slow dynamics between the two phases and compared the numerical results with those from the DNA polymer physics-based worm-like chain model. The supercoiling dynamics, including the nucleation, diffusion, and hopping of plectonemes, have been well represented and reproduced, using the two-phase dynamic model, at trivial computational costs. Our current developments, therefore, can be implemented to explore multiscale physical mechanisms of the DNA supercoiling-dependent physiological processes.