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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
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Quantification of topological coupling between DNA superhelicity and G-quadruplex formation
Sangeetha Selvam1, Deepak Koirala, Zhongbo Yu
1Department of Chemistry and Biochemistry, Kent State University , Kent, Ohio 44242, United States.
Journal of the American Chemical Society
|September 13, 2014
Summary
DNA superhelicity influences G-quadruplex formation, impacting gene transcription. Novel magneto-optical tweezers quantify this topological coupling, revealing DNA flexibility changes and G-quadruplex population dynamics.
Area of Science:
- Molecular Biology
- Biophysics
- Genetics
Background:
- Transcription regulation is influenced by DNA topology.
- G-quadruplexes are DNA secondary structures with roles in gene regulation.
- Quantifying the interplay between DNA superhelicity and G-quadruplex formation has been challenging.
Purpose of the Study:
- To directly quantify the topological coupling between DNA superhelicity and G-quadruplex formation.
- To investigate how DNA superhelicity affects DNA flexibility and G-quadruplex population.
- To provide molecular-level evidence for topology-mediated transcription modulation.
Main Methods:
- Development and application of novel magneto-optical tweezers.
- Combining nanometer resolution of optical tweezers with magnetic tweezers manipulation.
- Measuring DNA flexibility and G-quadruplex population under varying superhelicity conditions (σ).
Main Results:
- DNA flexibility increases with positive superhelicity (σ).
- G-quadruplex population increases from 2.4% at σ = 0.1 to 12% at σ = -0.03.
- G-quadruplex population rapidly increases to 23% at σ < -0.05, correlating with DNA melting.
Conclusions:
- DNA superhelicity directly modulates G-quadruplex formation.
- G-quadruplex formation is linked to DNA melting under specific topological stress.
- Magneto-optical tweezers offer a powerful tool for studying mechanochemical aspects of biological macromolecules.
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