Long-range oxidative damage in duplex DNA: the effect of bulged G in a G-C tract and tandem G/A mispairs.
Two series of duplex DNA oligomers were prepared having an anthraquinone derivative (AQ) covalently linked at a 5'-terminus. Irradiation of the AQ at 350 nm leads to injection of an electron hole (radical cation) into the DNA. The radical cation migrates through the DNA causing reaction primarily at G(n) sequences. In one series, GA tandem mispairs are inserted between GG steps to assess the effect of the mispair on the transport of the radical cation, reaction (damage) caused by the radical cation at the mispair, and repair of the resulting damage by formamidopyrimidine DNA glycosylase (Fpg). In the second series, a bulged guanine in a G3C2 sequence is interposed between the GG steps. These experiments reveal that neither G/A tandem mispairs nor bulged guanines are significant barriers to long-range charge migration in DNA. The radical cation does not cause reaction at guanines in the G/A tandem mispair. Reaction does occur at the bulged guanine, but it is repaired by Fpg.
Boone
Edna
E
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Schuster
Gary B
GB
D000225:Adenine / Q000378:metabolism; D000880:Anthraquinones / Q000378:metabolism; D020137:Base Pair Mismatch / Q000235:genetics*; D002412:Cations / Q000378:metabolism; D002942:Circular Dichroism; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D004579:Electron Transport; D004583:Electrons; D020862:GC Rich Sequence / Q000235:genetics*; D006147:Guanine / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D018384:Oxidative Stress; D010782:Photolysis; D020080:Tandem Repeat Sequences / Q000235:genetics; D013696:Temperature
D000880:Anthraquinones; D002412:Cations; D006147:Guanine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D000225:Adenine