The presence of two distinct 8-oxoguanine repair enzymes in human cells

Their potential complementary roles in preventing mutation

Tapas Hazra, Tadahide Izumi, Lindsay Maidt, Robert A. Floyd, Sankar Mitra

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5116-5122
Number of pages7
JournalNucleic Acids Research
Volume26
Issue number22
StatePublished - Nov 15 1998

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Mutation
DNA
Enzymes
Reactive Oxygen Species
DNA Glycosylases
DNA Mismatch Repair
Thymine
Cytosine
DNA-Binding Proteins
Guanine
Adenine
Ionizing Radiation
Cell Extracts
Complementary DNA
8-hydroxyguanine
Neoplasms
8-oxodeoxyguanosine triphosphate

ASJC Scopus subject areas

  • Genetics

Cite this

The presence of two distinct 8-oxoguanine repair enzymes in human cells : Their potential complementary roles in preventing mutation. / Hazra, Tapas; Izumi, Tadahide; Maidt, Lindsay; Floyd, Robert A.; Mitra, Sankar.

In: Nucleic Acids Research, Vol. 26, No. 22, 15.11.1998, p. 5116-5122.

Research output: Contribution to journalArticle

Hazra, Tapas ; Izumi, Tadahide ; Maidt, Lindsay ; Floyd, Robert A. ; Mitra, Sankar. / The presence of two distinct 8-oxoguanine repair enzymes in human cells : Their potential complementary roles in preventing mutation. In: Nucleic Acids Research. 1998 ; Vol. 26, No. 22. pp. 5116-5122.
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