A Single Ribonucleotide and the Various Possibilities for Charge Transfer Modulation Through ds-DNA: A Density...

Area of Science:

• Biochemistry
• Computational Chemistry
• Molecular Biology

Background:

• Ribonucleotides are sometimes incorporated into DNA during replication.
• If not repaired, these ribonucleotides can alter DNA structure and interfere with charge transfer, crucial for DNA repair and replication processes.
• These structural and electronic changes may affect genome stability.

Purpose of the Study:

• To theoretically investigate the impact of a single embedded riboadenosine on the structure, electronic properties, and charge-transfer capabilities of double-stranded DNA (ds-DNA).
• To analyze four distinct forms of the modified ribonucleotide site: native linkage (R-DNA), cyclic phosphate intermediate (IM-R-DNA), rearranged linkage (RE-R-DNA), and single-strand break (SSB-R-DNA).

Main Methods:

• Utilized M06-2X/6-31++G**//M06-2X/D95** theoretical level of theory in aqueous phase.
• Calculated spatial geometry, electronic properties (ionization potential, electron affinity), and charge migration pathways.
• Focused on the effects of the modified linkage on base stacking and electronic interactions within the ds-DNA oligonucleotide.

Main Results:

• A single riboadenosine significantly perturbs ds-DNA geometry, particularly base stacking and overlap, with rearrangements and cleavage reducing stacking energy by ~7 kcal•mol⁻¹.
• Different forms exhibit varied electronic properties: R-DNA has high ionization potential and low electron affinity, while SSB-R-DNA shows the opposite, indicating greater charge stabilization.
• Charge migration patterns are altered, with specific base pairs favored as electron or hole sinks depending on the ribonucleotide's linkage and modification state.

Conclusions:

• Even a single ribonucleotide's linkage chemistry can substantially alter charge migration in ds-DNA.
• These alterations in charge transfer may influence the efficiency of DNA repair mechanisms and overall genome stability.
• The study highlights the importance of understanding ribonucleotide incorporation and repair in maintaining genomic integrity.