Antimutagenic role of base-excision repair enzymes upon free radical-induced DNA damage.
As a consequence of oxidative stress, reactive oxygen species are generated in the cells. They interact with DNA and induce various modifications. Among them, oxidised purines (such as C8-oxoguanine and purines whose imidazole ring is opened), oxidised pyrimidines (such as thymine and cytosine glycols, ring saturated and fragmented pyrimidines), ethenobases and hypoxanthine. These various lesions have either miscoding properties or are blocks for DNA and RNA polymerases during replication and transcription, respectively. Most of these lesions are repaired by the base excision pathway in which the first step is mediated by specific DNA glycosylases. We review the various glycosylases involved in the repair of oxidised bases in Escherichia coli. The Fpg protein (formamidopyrimidine-DNA glycosylase) contains a zinc finger and excises oxidised purines whereas the Nth protein excises oxidised pyrimidines. The Nei protein excises a comparable spectra of pyrimidines and is believed to act as a back up enzyme to the Nth protein. The hypoxanthine-DNA glycosylase excises hypoxanthine residue and is one of the various activities of the AlkA protein (including formyluracil and ethenopurines residues). The Nfo protein was shown to have a novel activity that incises 5' to an alpha-deoxyadenosine residue (the anomer of deoxyadenosine formed by gamma-irradiation). The mechanism of action of the Fpg and Nth proteins are discussed. The properties of the human counterpart of the Fpg and Nth proteins the hNth and OGG1 proteins, respectively are also reviewed.
Laval
J
J
Groupe Reparation des lesions Radio- et Chimio-Induites, URA 147 CNRS, Institut Gustave Roussy, 94805 Villejuif Cedex, France. jlaval@igr.fr
Jurado
J
J
Saparbaev
M
M
Sidorkina
O
O
D016587:Antimutagenic Agents / Q000494:pharmacology*; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D005609:Free Radicals; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000502:physiology*
D016587:Antimutagenic Agents; D005609:Free Radicals; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases