The Electronic Property Differences between dA::dG and dA::dG^oxo. A Theoretical Approach

Area of Science:

• Molecular Biology
• Biochemistry
• Computational Chemistry

Background:

• Oxidative damage to DNA can lead to mutations, such as AT→GC and GC→AC transversions.
• DNA glycosylases, including OGG1 and MutY, evolved to repair such damage.
• MutY specifically removes adenine from dA::dG^oxo and dA:dG mispairs, with a preference for dA::dG^oxo.

Purpose of the Study:

• To investigate the structural and electronic properties of nucleoside pairs in aqueous solution.
• To understand the influence of solvent relaxation on these properties.
• To elucidate the electronic basis for MutY's preferential recognition of dA::dG^oxo over dA:dG.

Main Methods:

• Theoretical calculations of nucleoside pairs (dA:dG, dC:::dG^oxo, dC:::dG, dA::dG^oxo) in the aqueous phase.
• Analysis of structural and electronic properties.
• Evaluation of solvent relaxation effects.

Main Results:

• The dA::dG^oxo nucleoside pair exhibits lower ionization potential and higher electron affinity compared to the dA:dG pair.
• These electronic differences are observed in both vertical and adiabatic modes.
• Solvent relaxation effects were considered in the theoretical analysis.

Conclusions:

• The electronic properties of dA::dG^oxo predispose it to electron trapping.
• This finding supports the preferential recognition of dA::dG^oxo by MutY's [Fe-S] cluster over dA:dG.
• The study provides insights into the molecular mechanisms of DNA repair.