Nonequilibrium dynamics and action at a distance in transcriptionally driven DNA supercoiling

Yair A. G. Fosado*, Davide Michieletto, Chris A. Brackley, Davide Marenduzzo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We study the effect of transcription on the kinetics of DNA supercoiling in three dimensions by means of Brownian dynamics simulations of a single-nucleotide–resolution coarse-grained model for double-stranded DNA. By explicitly accounting for the action of a transcribing RNA polymerase (RNAP), we characterize the geometry and nonequilibrium dynamics of the ensuing twin supercoiling domains. Contrary to the typical textbook picture, we find that the generation of twist by RNAP results in the formation of plectonemes (writhed DNA) some distance away. We further demonstrate that this translates into an “action at a distance” on DNA-binding proteins; for instance, positive supercoils downstream of an elongating RNAP destabilize nucleosomes long before the transcriptional machinery reaches the histone octamer. We also analyze the relaxation dynamics of supercoiled double-stranded DNA, and characterize the widely different timescales of twist diffusion, which is a simple and fast process, and writhe relaxation, which is much slower and entails multiple steps.
Original languageEnglish
Article numbere1905215118
Pages (from-to)1-6
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number10
DOIs
Publication statusPublished - 1 Mar 2021

Keywords

  • DNA topology
  • supercoiling
  • transcription
  • nonequilibrium physics

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