Structure and in vitro replication of DNA templates containing 7,8-dihydro-8-oxoadenine

Nucleic Acids Res. 1991 Apr 25;19(8):1753-8. doi: 10.1093/nar/19.8.1753.

Abstract

Adenine residues in DNA are oxidized under the action of ionizing radiation at the C-8 position to give 7,8-dihydro-8-oxoadenine. The formation of this lesion can be considered a cause of mutations and carcinogenesis. Oligodeoxyribonucleotides 39 and 47 bases long containing a single 7,8-dihydro-8-oxoadenine (8-hydroxyadenine) residue were synthesized by using nucleoside phosphoramidites. They were used as templates to study the copies obtained in vitro by the Klenow fragment and the thermostable Taq DNA polymerase. 7,8-Dihydro-8-oxoadenine does not block the replication and thymine is incorporated opposite the damage. The modifications of the DNA duplex conformation provoked by 7,8-dihydro-8-oxoadenine are minor. 1H-NMR spectroscopy shows that the duplex is in a B form, the sugar in a normal position in the helix and the modified base in the anti position. NMR confirms that 7,8-dihydro-8-oxoadenine exists predominantly in the keto form.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemistry
  • Adenine / metabolism
  • Base Composition
  • Base Sequence
  • DNA / biosynthesis
  • DNA / chemistry*
  • DNA / genetics
  • DNA Replication*
  • Electrophoresis, Polyacrylamide Gel
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemical synthesis
  • Oligodeoxyribonucleotides / genetics
  • Oxidation-Reduction
  • Protons
  • Templates, Genetic

Substances

  • Oligodeoxyribonucleotides
  • Protons
  • 8-hydroxyadenine
  • DNA
  • Adenine