Dynamics of supercoiled knotted DNA: largescale rearrangements and persistent multistrand interlocking

Catalytic processes in bacterial plasmid introduce knots and supercoiling. The effect of the latter has been separately and extensively studied, however much less is known about their concurrent action. Thus, to study the kinetic and metric changes introduced by complex knots and supercoiling in 2kbp-long DNA rings, we use molecular dynamics simulation and oxDNA, a mesoscopic DNA model, finding several unexpected results. First, two distinct states dominate the conformational ensemble, they differ in branchedness and knot size; secondly, fluctuations between these states are as fast as the metric relaxation of unknotted rings. Nevertheless, certain boundaries of knotted and plectonemically wound regions can persist over much longer timescales. These regions involve multiple strands that are interlocked by the cooperative action of topological and supercoiling constraints. Their long liver character may be relevant for the simplifying action of topoisomerases.