Twin Supercoil Domain Couples the Dynamics of Molecular Motors and Plectonemes during Bacterial DNA Transcription and Replication

Abstract

The genomic DNA of most bacteria is significantly underwound, which constrains the DNA molecule to adopt a branched plectoneme geometry. Moreover, biological functions like replication and transcription require that the two DNA strands be transiently opened, which generates waves of positive (respectively, negative) supercoiling downstream (respectively, upstream) of the molecular motor, a feature known as Twin Supercoiled Domain (TSD). In this work, we used coarse-grained modeling and Brownian dynamics simulations to investigate the interactions between a TSD and the plectonemes of bacterial DNA. Simulations indicate that the slithering dynamics of short plasmids is not significantly affected by a TSD. In contrast, the TSD potently stimulates the spontaneous displacement modes (diffusion and growth/shrinkage) of the plectonemes of longer DNA molecules. This results in the motor trailing a growing plectoneme behind itself if it translocates more slowly than the maximum slithering speed of plectonemes. In contrast, if the motor translocates more rapidly than this limit, then quasi-immobile plectonemes nucleate almost periodically upstream of the motor, grow up to several kbp, detach from the motor, shrink, and disappear. The effect of an eventual static bend imposed by the motor and of the topological barriers was also investigated.