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Updated: Oct 12, 2025

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
The polarization dependence of 2D IR cross-peaks distinguishes parallel-stranded and antiparallel-stranded DNA
David A Price1, Poornima Wedamulla1, Tayler D Hill1
1School of Chemical and Biomolecular Sciences, Southern Illinois University Carbondale, 1245 Lincoln Drive MC 4409, Carbondale, IL 62901, United States.
Abstract:
Guanine-rich nucleic acid sequences have a tendency to form four-stranded non-canonical motifs known as G-quadruplexes. These motifs may adopt a wide range of structures characterized by size, strand orientation, guanine base conformation, and fold topology. Using three K+-bound model systems, we show that vibrational coupling between guanine C6 = O and ring modes varies between parallel-stranded and antiparallel-stranded G-quadruplexes, and that such structures can be distinguished by comparison of the polarization dependences of cross-peaks in their two-dimensional infrared (2D IR) spectra. Combined with previously defined vibrational frequency trends, this analysis reveals key features of a 30-nucleotide unimolecular variant of the Bcl-2 proximal promoter that are consistent with its reported structure. This study shows that 2D IR spectroscopy is a convenient method for analyzing G-quadruplex structures that can be applied to complex sequences where traditional high-resolution methods are limited by solubility and disorder.
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