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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

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G-quadruplex structural transition driven by a platinum compound.

Wenting Liu1, Bo-Chen Zhu1, Liu-Yi Liu1

  • 1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou 510275, China.

Nucleic Acids Research
|June 29, 2022
PubMed
Summary
This summary is machine-generated.

This study reveals how the platinum(II) compound Pt-phen drives G-quadruplex (G4) transitions, detailing distinct molecular pathways and complex formations. Understanding these ligand-driven G4 transitions is crucial for biological regulation.

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Chemical Biology

Background:

  • G-quadruplex (G4) structures are crucial in biological regulation.
  • Ligand interactions can modify G4 structures, but transition pathways remain poorly understood.

Purpose of the Study:

  • To elucidate the distinct molecular pathways of G-quadruplex (G4) transitions induced by a platinum(II) compound, Pt-phen.
  • To determine the structural basis of ligand-driven G4 transitions.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the structures of Pt-phen-MYC G4 complexes.
  • Three-dimensional structures of 1:1 5'-end binding, 1:1 3'-end binding, and 2:1 Pt-phen-MYC G4 complexes were elucidated.

Main Results:

  • Pt-phen drives G4 transitions even at low ratios, forming distinct 1:1 and 2:1 complexes.
  • The pathway is dependent on potassium ion (K+) concentration, with a stable T:T:A triad formation influencing binding order.
  • Edgewise-loop/G-tetrad sandwich structures and T:T:A triad stabilization are key to transition pathways.

Conclusions:

  • This is the first study to reveal molecular structures of small molecule-driven G4 transitions.
  • Ligand-driven G4 transition is a dynamic process involving rapid structural changes and the formation of multiple complexes.