Properties and biological functions of the NTH and FPG proteins of Escherichia coli: two DNA glycosylases that repair oxidative damage in DNA.
Oxidative damage to DNA is one of the most important causes of spontaneous mutations and may play a role in aging and related diseases, such as cancer, in humans. Oxidative damage results from the attack of biomolecules by free radicals and reactive oxygen species formed as byproducts of normal cell metabolism or during oxidative stress. To counteract the lethal and mutagenic effects of oxidative lesions in DNA, cells have developed defence strategies including DNA repair systems. In Escherichia coli, the repair of oxidized bases in DNA is mostly mediated by the base excision repair pathway. The first step in this DNA repair pathway is catalysed either by the NTH protein which excises oxidized pyrimidines or by the FPG protein which excises oxidized purines. The nucleotide excision repair pathway mediated by the UvrABC complex may also play a role when the DNA glycosylases are inactive or saturated. This review summarizes the structural and catalytic properties of the NTH and FPG proteins of Escherichia coli and presents evidence to indicate that these two enzymes constitute an important component of the cellular defence against oxidative stress in prokaryotes and eukaryotes.
Boiteux
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LA 147 CNRS, U140 INSERM, Institut Gustave-Roussy, Villejuif, France.
D000595:Amino Acid Sequence; D004249:DNA Damage; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D010782:Photolysis; D013379:Substrate Specificity
D029968:Escherichia coli Proteins; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli