Long-range oxidative damage in DNA/RNA duplexes.
Oxidative damage as a result of DNA-mediated long-range charge transport occurs 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 strands were constructed containing tethered ethidium as a photooxidant. In photooxidation experiments, long-range oxidative damage to the ribose-containing strand of the oligonucleotide duplexes was examined. Hole injection by photoexcited ethidium followed by radical migration to oxidatively susceptible guanines afforded significant damage on ribose-containing strands at long range ( approximately 35 A). This damage does not differ substantially in yield and location from that found in B-DNA duplexes. No oxidative damage was found upon photooxidation of DNA/RNA duplexes containing tethered metallointercalator, despite the ability of the rhodium complex to promote oxidative damage at a distance in DNA duplexes. This result is attributed to 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 nucleic acids of different comformations is considered in light of modeling studies that show interstrand base-base overlap between the opposing, complementary 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.
Odom
D T
DT
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Barton
J K
JK
D001482:Base Composition; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D003855:Deoxyribose / Q000378:metabolism / Q000528:radiation effects; D018900:Dinucleotide Repeats / Q000528:radiation effects; D004996:Ethidium / Q000378:metabolism; D006147:Guanine / Q000378:metabolism / Q000528:radiation effects; D007364:Intercalating Agents / Q000378:metabolism; D009692:Nucleic Acid Heteroduplexes / Q000378:metabolism* / Q000528:radiation effects; D009838:Oligodeoxyribonucleotides / Q000378:metabolism / Q000528:radiation effects; D010084:Oxidation-Reduction; D012313:RNA / Q000378:metabolism* / Q000528:radiation effects; D012238:Rhodium / Q000378:metabolism; D012266:Ribose / Q000378:metabolism / Q000528:radiation effects
D007364:Intercalating Agents; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D003855:Deoxyribose; D006147:Guanine; D012313:RNA; D012266:Ribose; D004247:DNA; D012238:Rhodium; D004996:Ethidium