Consistent rationalization of type-2 topoisomerases' unknotting, decatenating, supercoil-relaxing actions and their scaling relation

How type-2 topoisomerases discern global topology from local properties of DNA is not known precisely but the hypothesis that the enzymes selectively pass double-helix strands at hook-like juxtapositions is promising. Building upon an investigation of unknotting and decatenating using an improved wormlike DNA model, here we focus primarily on the enzymes' action in narrowing the distribution of linking number (Lk) in supercoiled DNA. Consistent with experiments, with selective passage at a hooked juxtaposition, the simulated narrowing factor R-Lk diminishes with decreasing DNA circle size but approaches an asymptotic R-Lk approximate to 1.7-1.8 for circle size greater than or similar to 3.5 kb. For the larger DNA circles, we found that (R-Lk - 1) approximate to 0.42 log(10) R-K approximate to 0.68 log(10) R-L and thus R-K approximate to (R-L)(1.6) holds for the computed R-Lk and knot and catenane reduction factors R-K and R-L attained by selective passage at different juxtaposition geometries. Remarkably, this general scaling relation is essentially identical to that observed experimentally for several type-2 topoisomerases from a variety of organisms, indicating that the different disentangling powers of the topoisomerases likely arise from variations in the hooked geometries they select. Taken together, our results suggest strongly that type-2 topoisomerases recognize not only the curvature of the G-segment but also that of the T-segment.Ministry of Science and Technology of China [2015CB910300]; Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council (NSERC) of Canada via CIHR operating grant [MOP-84281]; Natural Sciences and Engineering Research Council (NSERC) of Canada via NSERC discovery grant [216901]SCI(E)EIPubMedARTICLELiuZhiRong@pku.edu.cn; chan@arrhenius.med.toronto.edu353541032