Nonequilibrium dynamics and action at a distance in transcriptionally driven DNA supercoiling.
| Autor: | Fosado YAG; Department of Physics and Mathematics, Aoyama Gakuin University, Kanagawa 252-5258, Japan; gtzyair@gmail.com dmarendu@ph.ed.ac.uk., Michieletto D; Scottish Universities Physics Alliance, School of Physics and Astronomy, University of Edinburgh, Edinburgh, EH9 3FD, United Kingdom.; Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom., Brackley CA; Scottish Universities Physics Alliance, School of Physics and Astronomy, University of Edinburgh, Edinburgh, EH9 3FD, United Kingdom., Marenduzzo D; Scottish Universities Physics Alliance, School of Physics and Astronomy, University of Edinburgh, Edinburgh, EH9 3FD, United Kingdom; gtzyair@gmail.com dmarendu@ph.ed.ac.uk. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Mar 09; Vol. 118 (10). |
| DOI: | 10.1073/pnas.1905215118 |
| Abstrakt: | 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. Competing Interests: The authors declare no competing interest. |
| Databáze: | MEDLINE |
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