ANTIMUTAGENIC ROLE OF BASE-EXCISION REPAIR ENZYMES UPON FREE RADICAL-INDUCED DNA-DAMAGE

As a consequence of oxidative stress, reactive oxygen species are gene rated in the cells. They interact with DNA and induce various modifica tions. Among them, oxidised purines (such as C-8-oxoguanine and purine s whose imidazole ring is opened), oxidised pyrimidines (such as thymi ne and cytosine glycols, ring saturated and fragmented pyrimidines), e thenobases and hypoxanthine. These various lesions have either miscodi ng properties or are blocks for DNA and RNA polymerases during replica tion and transcription, respectively. Most of these lesions are repair ed by the base excision pathway in which the first step is mediated by specific DNA glycosylases. We review the various glycosylases involve d in the repair of oxidised bases in Escherichia coli. The Fpg protein (formamidopyrimidine-DNA glycosylase) contains a zinc finger and exci ses oxidised purines whereas the Nth protein excises oxidised pyrimidi nes. The Nei protein excises a comparable spectra of pyrimidines and i s believed to act as a back up enzyme to the Nth protein. The hypoxant hine-DNA glycosylase excises hypoxanthine residue and is one of the va rious activities of the AlkA protein (including formyluracil and ethen opurines residues). The Nfo protein was shown to have a novel activity that incises 5' to an alpha-deoxyadenosine residue (the anomer of deo xyadenosine formed by gamma-irradiation). The mechanism of action of t he Fpg and Nth proteins are discussed. The properties of the human cou nterpart of the Fpg and Nth proteins the hNth and OGG1 proteins, respe ctively are also reviewed. (C) 1998 Elsevier Science B.V. All rights r eserved.