G-quadruplex DNA (G4-DNA), a noncanonical tetrahelical nucleic acid structure stabilized by stacked G-quartets via Hoogsteen hydrogen bonding, plays critical roles in genomic regulation and disease pathogenesis. Current methodologies for detecting these structures face limitations in specificity, spatiotemporal resolution, and live-cell applicability. To address these challenges, we engineered G4-Flame, a genetically encoded fluorescent biosensor utilizing circularly permuted fluorescent protein technology. By strategically positioning a G4-specific binding domain proximal to the fluorophore of circularly permuted YFP (cpYFP), G4-Flame achieves real-time, high-resolution visualization of G4-DNA dynamics in living systems, with specificity across diverse G4 conformations. Experimental validation revealed distinct spatiotemporal patterns of G4-DNA during the cell cycle: nuclear G4-DNA levels peaked during the S phase, while mitochondrial G4-DNA was found to suppress the expression of mitochondrial-encoded genes. Clinically, serum analysis revealed significantly elevated G4-DNA levels in cancer patients compared to healthy controls. This work establishes G4-Flame as a transformative tool for investigating G4-DNA spatiotemporal regulation and advances its potential as a biomarker for early cancer detection, bridging fundamental research with clinical translation.
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Ronghui Liu
Tao Wang
C. X. Wang
Nucleic Acids Research
University of Science and Technology of China
Harbin Medical University
Hefei Institutes of Physical Science
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Liu et al. (Thu,) studied this question.
www.synapsesocial.com/papers/69c4cc85fdc3bde448917da4 — DOI: https://doi.org/10.1093/nar/gkag179
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