The presence of two distinct 8-oxoguanine repair enzymes in human cells: their potential complementary roles in preventing mutation

Nucleic Acids Res. 1998 Nov 15;26(22):5116-22. doi: 10.1093/nar/26.22.5116.


8-Oxoguanine (8-oxoG), induced by reactive oxygen species (ROS) and ionizing radiation, is arguably the most important mutagenic lesion in DNA. This oxidized base, because of its mispairing with A, induces GC-->TA transversion mutations often observed spontaneously in tumor cells. The human cDNA encoding the repair enzyme 8-oxoG-DNA glycosylase (OGG-1) has recently been cloned, however, its activity was never detected in cells. Here we show that the apparent lack of this activity could be due to the presence of an 8-oxoG-specific DNA binding protein. Moreover, we demonstrate the presence of two antigenically distinct OGG activities with an identical reaction mechanism in human cell (HeLa) extracts. The 38 kDa OGG-1, identical to the cloned enzyme, cleaves 8-oxoG when paired with cytosine, thymine and guanine but not adenine in DNA. In contrast, the newly discovered 36 kDa OGG-2 prefers 8-oxoG paired with G and A. We propose that OGG-1 and OGG-2 have distinct antimutagenic functions in vivo . OGG-1 prevents mutation by removing 8-oxoG formed in DNA in situ and paired with C, while OGG-2 removes 8-oxoG that is incorporated opposite A in DNA from ROS-induced 8-oxodGTP. We predict that OGG-2 specifically removes such 8-oxoG residues only from the nascent strand, possibly by utilizing the same mechanism as the DNA mismatch repair pathway.

Publication types

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

MeSH terms

  • Carbon-Oxygen Lyases / metabolism
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA Damage
  • DNA Glycosylases
  • DNA Ligases / genetics*
  • DNA Ligases / metabolism*
  • DNA Repair / genetics*
  • DNA Repair / physiology*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • GTP-Binding Proteins / metabolism
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • HeLa Cells
  • Humans
  • Mutation*
  • N-Glycosyl Hydrolases / metabolism


  • 8-hydroxyguanine
  • Guanine
  • DNA
  • Deoxyribonuclease IV (Phage T4-Induced)
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • GTP-Binding Proteins
  • Carbon-Oxygen Lyases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • DNA Ligases