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Updated: Apr 26, 2026
Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
A newly identified G-quadruplex as a potential target regulating Bcl-2 expression
Hongxia Sun1, Junfeng Xiang1, Yunhua Shi2
1Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
Background:
A new G-quadruplex structure located in the B-cell CLL/lymphoma 2 (Bcl-2) P1 promoter and its physiological function related to Bcl-2 transcription have been studied to find a potential anticancer therapeutic target.
Methods:
Absorption, polyacrylamide gel electrophoresis, fluorescence, circular dichroism, and nuclear magnetic resonance spectra have been employed to determine G-quadruplex structure and the interaction between G-quadruplex and phenanthrolin-dicarboxylate. Real time polymerase chain reaction and luciferase assay were done to assess the physiological function of the G-quadruplex structure.
Results:
The UV-melting and polyacrylamide gel electrophoresis studies show that the p32 DNA sequence forms an intramolecular G-quadruplex structure. Circular dichroism and nuclear magnetic resonance spectra indicate that the G-quadruplex is a hybrid-type structure with four G-tetrads. Fluorescence spectra show that a phenanthroline derivative has a higher binding affinity for p32 G-quadruplex than duplex. Further circular dichroism and nuclear magnetic resonance studies indicate that the phenanthroline derivative can regulate p32 G-quadruplex conformation. Real time polymerase chain reaction and luciferase assays show that the phenanthroline derivative has down-modulated Bcl-2 transcription activity in a concentration-dependent manner. However, no such effect was observed when p32 G-quadruplex was denatured through base mutation.
Conclusion:
The newly identified G-quadruplex located in the P1 promoter of Bcl-2 oncogene is intimately related with Bcl-2 transcription activity, which may be a promising anticancer therapeutic target.
General Significance:
The newly identified G-quadruplex in the Bcl-2 P1 promoter may be a novel anticancer therapeutic target.
Insights
Researchers discovered a novel G-quadruplex in the Bcl-2 P1 promoter. This structure regulates Bcl-2 transcription and shows potential as an anticancer therapeutic target.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- A G-quadruplex structure in the B-cell CLL/lymphoma 2 (Bcl-2) P1 promoter was investigated.
- Its role in Bcl-2 transcription was studied to identify potential anticancer targets.
Purpose of the Study:
- To characterize a novel G-quadruplex structure in the Bcl-2 P1 promoter.
- To assess its physiological function and interaction with small molecules.
- To evaluate its potential as an anticancer therapeutic target.
Main Methods:
- G-quadruplex structure determination using UV-melting, polyacrylamide gel electrophoresis, circular dichroism, and nuclear magnetic resonance.
- Interaction studies with a phenanthroline derivative using fluorescence spectroscopy.
- Functional assessment via real-time polymerase chain reaction and luciferase assays.
Main Results:
- The p32 DNA sequence forms an intramolecular hybrid-type G-quadruplex.
- A phenanthroline derivative binds with high affinity and modulates the G-quadruplex conformation.
- The phenanthroline derivative down-regulates Bcl-2 transcription in a concentration-dependent manner.
- Functional effects were dependent on the intact G-quadruplex structure.
Conclusions:
- A novel G-quadruplex in the Bcl-2 P1 promoter is intrinsically linked to Bcl-2 transcription.
- This G-quadruplex represents a promising novel anticancer therapeutic target.
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