Long-range oxidative damage in DNA/RNA duplexes

Oxidative damage as a result of DNA-mediated long-range charge transport oc curs readily and at high yield in duplex DNA, and it is of interest whether similar damage can occur in duplex oligonucleotides that include both ribo - and deoxyribonucleotides. Assemblies containing RNA and mixed RNA-DNA str ands were constructed containing tethered ethidium as a photooxidant. In ph otooxidation experiments, long-range oxidative damage to the ribose-contain ing strand of the oligonucleotide duplexes was examined. Hole injection by photoexcited ethidium followed by radical migration to oxidatively suscepti ble guanines afforded significant damage on ribose-containing strands at lo ng range (similar to 35 Angstrom). This damage does not differ substantiall y in yield and location from that found in B-DNA duplexes. No oxidative dam age was found upon photooxidation of DNA/RNA duplexes containing tethered m etal-lointercalator, despite the ability of the rhodium complex to promote oxidative damage at a distance in DNA duplexes. This result is attributed t o the poor coupling of the rhodium complex into the A-like RNA/DNA duplex. The ability for long-range charge transport to occur in double-stranded nuc leic acids of different comformations is considered in light of modeling st udies that show interstrand base-base overlap between the opposing, complem entary strands that make up RNA/DNA hybrid duplexes. Thus, the possibility of long-range radical migration to effect oxidative damage or signaling may be considered also in the context of transcriptional events.