Hole transfer energetics in structurally distorted DNA: the nucleosome core particle

Area of Science:

• Biophysics
• Quantum Chemistry
• Molecular Biology

Background:

• Long-range hole transport (HT) in DNA is crucial for biological processes.
• Guanine radical cation states are key to DNA HT dynamics.
• DNA is compacted into nucleosome core particles (NCPs) in eukaryotic nuclei.

Purpose of the Study:

• To investigate how electrostatic interactions and structural changes in NCPs affect DNA hole transfer energetics.
• To understand the influence of protein and water environments on guanine radical cation stability.

Main Methods:

• Utilized quantum-chemical calculations.
• Modeled electrostatic interactions between DNA nucleobases, protein, and water atoms.
• Assessed structural changes in DNA within NCPs.

Main Results:

• Structural distortions in DNA significantly impact guanine radical cation stability.
• DNA-histone contacts, especially arginine residues with the minor groove, destabilize specific guanine radical cation states.
• Electrostatic potentials from water and histone proteins alter preferred sites of hole stability.

Conclusions:

• Structural and electrostatic factors within NCPs are critical for modeling in vivo DNA HT.
• Histone-DNA interactions can perturb guanine sites, influencing DNA HT pathways.
• Accurate interpretation of experimental DNA HT findings requires considering these in vivo effects.