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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
838
8-Oxoguanine Disrupts G-Quadruplex DNA Stability and Modulates FANCJ AKKQ Peptide Binding
Laura Campbell1,2, Kaitlin Lowran2,3, Emma Cismas2
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Molecules (Basel, Switzerland)
|August 28, 2025
Summary
The FANCJ helicase
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Guanine-rich sequences form G-quadruplex (G4) structures.
- G4s can impede DNA replication and repair.
- FANCJ helicase resolves G4s, maintaining genome stability.
Purpose of the Study:
- Investigate FANCJ's recognition of 8-oxoguanine-modified G4s (8oxoG4s).
- Determine how sequence context, lesion position, and stability affect FANCJ binding.
- Elucidate the role of the FANCJ AKKQ motif in 8oxoG4 recognition.
Main Methods:
- Synthesized G4 sequences with 8-oxoguanine modifications.
- Measured peptide-G4 binding affinities using fluorescence spectroscopy.
- Assessed G4 conformation and stability via circular dichroism spectroscopy.
Main Results:
- FANCJ AKKQ binding affinity varied with 8oxoG position and sequence context.
- Specific G4 sequences (e.g., (GGGT)4, (TTAGGG)4) showed altered stability and binding.
- Potassium chloride and sodium chloride conditions modulated G4 stability and FANCJ interaction.
Conclusions:
- FANCJ binding to G4s and 8oxoG4s is influenced by oxidative damage location.
- The local sequence environment of G4 structures impacts FANCJ recognition.
- These findings refine models of FANCJ's role in resolving damaged G4 structures.
