PMID:10862773

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Citation

Hazra, TK, Izumi, T, Venkataraman, R, Kow, YW, Dizdaroglu, M and Mitra, S (2000) Characterization of a novel 8-oxoguanine-DNA glycosylase activity in Escherichia coli and identification of the enzyme as endonuclease VIII. J. Biol. Chem. 275:27762-7

Abstract

8-Oxoguanine (G*), induced by reactive oxygen species, is mutagenic because it mispairs with A. The major G*-DNA glycosylase (OGG), namely, OGG1 in eukaryotes, or MutM in Escherichia coli, excises G* when paired in DNA with C, G, and T, but not A, presumably because removal of G* from a G*.A pair would be mutagenic. However, repair of G* will prevent mutation when it is incorporated in the nascent strand opposite A. This could be carried out by a second OGG, OGG2, identified in yeast and human cells. We have characterized a new OGG activity in E. coli and then identified it to be endonuclease VIII (Nei), discovered as a damaged pyrimidine-specific DNA glycosylase. Nei shares sequence homology and reaction mechanism with MutM and is similar to human OGG2 in being able to excise G* when paired with A (or G). Kinetic analysis of wild type Nei showed that it has significant activity for excising G* relative to dihydrouracil. The presence of OGG2 type enzyme in both E. coli and eukaryotes, which is at least as efficient in excising G* from a G*.A (or G) pair as from a G*.C pair, supports the possibility of G* repair in the nascent DNA strand.

Links

PubMed Online version:10.1074/jbc.M004052200

Keywords

DNA Damage; DNA Repair; DNA-Formamidopyrimidine Glycosylase; Deoxyribonuclease (Pyrimidine Dimer); Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/metabolism; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli Proteins; Humans; Kinetics; N-Glycosyl Hydrolases/genetics; N-Glycosyl Hydrolases/isolation & purification; N-Glycosyl Hydrolases/metabolism; Oligodeoxyribonucleotides/chemistry; Recombinant Proteins/isolation & purification; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/enzymology; Substrate Specificity

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