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Transcribing RNA polymerases: Dynamics of twin supercoiled domains
1Laboratoire Interdisciplinaire de Physique, CNRS and Université Grenoble Alpes, St Martin d'Hères, France.
Biophysical Journal
|October 5, 2024
Summary
RNA polymerase (RNAP) transcription creates twin supercoiled domains (TSDs) in DNA. Simulations show negative supercoiled plectonemes form upstream of RNAP, differing from the classic TSD model.
Area of Science:
- Molecular Biology
- Biophysics
- Computational Biology
Background:
- Gene transcription by RNA polymerase (RNAP) involves DNA unwinding, altering DNA supercoiling.
- The twin supercoiled domain (TSD) model predicts positive supercoiling ahead and negative behind RNAP.
- Understanding DNA torsional dynamics during transcription is crucial for gene regulation.
Purpose of the Study:
- To investigate the detailed torsional dynamics of circular DNA during RNAP transcription.
- To explore how DNA superhelical density and RNAP rotational properties influence TSD formation.
- To compare simulation results with the established TSD model.
Main Methods:
- Brownian dynamics simulations were employed.
- A specialized coarse-grained model of DNA and RNAP was utilized.
- Simulations analyzed the effects of varying superhelical density and RNAP twist injection rate relative to relaxation speed.
Main Results:
- Simulation results revealed complex behaviors that deviate from the simple TSD picture.
- Under conditions of slow rotational relaxation and physiological negative supercoiling, positive plectonemes did not form ahead of RNAP.
- Instead, negative supercoiled plectonemes formed upstream, grew, detached, and destabilized.
Conclusions:
- The formation and behavior of supercoiled domains during transcription are more complex than the basic TSD model suggests.
- RNAP transcription dynamics are highly dependent on DNA supercoiling levels and the balance between twist injection and relaxation.
- Topological barriers significantly influence the dynamics of these supercoiled domains.
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