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

Ribonucleotides are frequently incorporated into DNA during the replication of genetic information and, if missed during ribonucleotide excision repair, they may undergo phosphodiester bond rearrangement or cleavage. These changes can in turn lead to deformation of the spatial geometry of the local double helix and potentially interfere with charge transfer through ds-DNA. This process is believed to support long-range communication between proteins involved in genome replication and repair. This study theoretically explores how a single embedded riboadenosine (A₃) affects the structure, electronic properties, and charge-transfer properties of double-stranded DNA ([A₁G₂A₃G₄A₅]*[T₅C₄T₃C₂T₁]). In particular, the study focuses on four products formed at the ribonucleotide site: native 3',5'-linkage (R-DNA), the 2',3'-cyclic phosphate intermediate (IM-R-DNA), rearranged 2',5-linked (RE-R-DNA), and the single-strand-break cleavage product (SSB-R-DNA). This theoretical investigation was performed at the M06-2X/6-31++G**//M06-2X/D95** level of theory in the aqueous phase. Significant spatial geometry perturbations were found at the central part of ds-oligonucleotides, i.e., the A₃T₃|G₄C₂ region, where the modified linkage affected the base overlap and stacking interactions most strongly; in the rearranged and cleaved forms, stacking at this site decreased by about 7 kcal•mol^-1 relative to native DNA. Global electronic analysis showed that R-DNA had the highest ionisation potential and the lowest electron affinity, whereas SSB-R-DNA displayed the lowest adiabatic ionisation potential and the highest adiabatic electron affinity, indicating a much greater tendency to stabilise excess charge. At the base-pair level, G₂C₄ was usually the preferred hole sink, except in RE-R-DNA, where G₄C₂ was favoured. In contrast, electron localisation was generally favoured at G₄C₂, while, in SSB-R-DNA, the A₃T₃ pair became the most favourable electron-accepting site. Overall, the results show that even a single ribonucleotide, depending on its linkage chemistry, can substantially reshape charge migration through ds-DNA and may therefore influence lesion recognition, repair efficiency, and genome stability.