Large-Scale Conformational Transitions in Supercoiled DNA Revealed by Coarse-Grained Simulation
Brad A Krajina1, Andrew J Spakowitz2
1Department of Chemical Engineering, Stanford University, Stanford, California.
Biophysical Journal
|October 6, 2016
Summary
Supercoiled DNA undergoes distinct structural changes at biologically relevant scales, revealing three key conformational regimes. This research provides a physical basis for DNA organization and its link to gene regulation.
Area of Science:
- Biophysics
- Molecular Biology
- Genomics
Background:
- Topological constraints, particularly DNA supercoiling, are crucial for genome regulation and organization.
- Understanding DNA organization at biological length scales presents a significant physical challenge.
Purpose of the Study:
- To develop a coarse-grained simulation method for predicting supercoiled DNA conformations.
- To investigate conformational transitions in supercoiled DNA across biologically relevant length scales and supercoiling densities.
Main Methods:
- Developed a coarse-grained simulation approach for supercoiled DNA.
- Simulated ring DNA molecules (approx. 10 kilobases) to model topological domains in *E. coli*.
Main Results:
- Identified three distinct supercoiling conformational regimes: chiral coils, extended plectonemes, and branched hyper-supercoils.
- Observed large-scale conformational transitions driven by supercoiling.
- Captured the nonmonotonic relationship between DNA size and supercoiling degree.
Conclusions:
- The study provides a physical explanation for observed conformational transitions in supercoiled DNA.
- Findings align with scales relevant to transcription-coupled DNA remodeling in bacteria.
- Results suggest implications for the interplay between transcription and topology in bacterial chromosome organization.
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