Repair of hydantoins, one electron oxidation product of 8-oxoguanine, by DNA glycosylases of Escherichia coli

Tapas K. Hazra, James G. Muller, Raymond C. Manuel, Cynthia J. Burrows, R. Stephen Lloyd, Sankar Mitra

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

8-Oxoguanine (8-oxoG), induced by reactive oxygen species and arguably one of the most important mutagenic DNA lesions, is prone to further oxidation. Its one-electron oxidation products include potentially mutagenic guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) because of their mispairing with A or G. All three oxidized base-specific DNA glycosylases of Escherichia coli, namely endonuclease III (Nth), 8-oxoG-DNA glycosylase (MutM) and endonuclease VIII (Nei), excise Gh and Sp, when paired with C or G in DNA, although Nth is less active than the other two. MutM prefers Sp and Gh paired with C (Kcat/Km of 0.24-0.26 min-1 nM-1), while Nei prefers G over C as the complementary base (kcat/Km -0.15-0.17 min-1 nM-1). However, only Nei efficiently excises these paired with A. MutY, a 8-oxoG·A(G)-specific A(G)-DNA glycosylase, is inactive with Gh(Sp)·A/G-containing duplex oligonucleotide, in spite of specific affinity. It inhibits excision of lesions by MutM from the Gh·G or Sp· pair, but not from Gh·C and Sp·C pairs. In contrast, MutY does not significantly inhibit Nei for any Gh(Sp) base pair. These results suggest a protective function for MutY in preventing mutation as a result of A (G) incorporation opposite Gh(Sp) during DNA replication.

Original languageEnglish (US)
Pages (from-to)1967-1974
Number of pages8
JournalNucleic acids research
Volume29
Issue number9
DOIs
StatePublished - May 1 2001

ASJC Scopus subject areas

  • Genetics

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