The effect of the 2-amino group of 7,8-dihydro-8-oxo-2'-deoxyguanosine on translesion synthesis and duplex stability

Nucleic Acids Res. 2005 Mar 18;33(5):1637-43. doi: 10.1093/nar/gki305. Print 2005.


Replication of DNA containing 7,8-dihydro-8-oxo-2'-deoxyguanosine (OxodG) gives rise to G --> T transversions. The syn-isomer of the lesion directs misincorporation of 2'-deoxyadenosine (dA) opposite it. We investigated the role of the 2-amino substituent on duplex thermal stability and in replication using 7,8-dihydro-8-oxo-2'-deoxyinosine (OxodI). Oligonucleotides containing OxodI at defined sites were chemically synthesized via solid phase synthesis. Translesion incorporation opposite OxodI was compared with 7,8-dihydro-8-oxo-2'-deoxyguanosine (OxodG), 2'-deoxyinosine (dI) and 2'-deoxyguanosine (dG) in otherwise identical templates. The Klenow exo- fragment of Escherichia coli DNA polymerase I incorporated 2'-deoxyadenosine (dA) six times more frequently than 2'-deoxycytidine (dC) opposite OxodI. Preferential translesion incorporation of dA was unique to OxodI. UV-melting experiments revealed that DNA containing OxodI opposite dA is more stable than when the modified nucleotide is opposed by dC. These data suggest that while duplex DNA accommodates the 2-amino group in syn-OxodG, this substituent is thermally destabilizing and does not provide a kinetic inducement for replication by Klenow exo-.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Amines / chemistry
  • Base Pairing
  • DNA / biosynthesis*
  • DNA / chemistry*
  • DNA Damage*
  • DNA Polymerase I / metabolism
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemistry*
  • Inosine / analogs & derivatives*
  • Inosine / chemistry
  • Kinetics
  • Nucleic Acid Denaturation
  • Oligodeoxyribonucleotides / biosynthesis
  • Oligodeoxyribonucleotides / chemical synthesis
  • Oligodeoxyribonucleotides / chemistry
  • Temperature


  • 7,8-dihydro-8-oxo-2'-deoxyinosine
  • Amines
  • Oligodeoxyribonucleotides
  • Inosine
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • DNA Polymerase I
  • Deoxyguanosine