期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1905215118
关键词
DNA topology; supercoiling; transcription; nonequilibrium physics
资金
- European Research Council [CoG 648050]
- Mexican National Council of Science and Technology PhD Grant [384582]
- Leverhulme Trust [ECF-2019-088]
The study investigates the effect of transcription on DNA supercoiling kinetics, revealing the formation of writhe structures at a distance from the transcribing RNA polymerase. Additionally, it shows that positive supercoils generated by RNAP can destabilize nucleosomes long before the transcriptional machinery reaches the histone octamer. The research also analyzes the relaxation dynamics of supercoiled DNA, highlighting the significantly different timescales of twist diffusion and writhe relaxation.
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.
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