Mechanism of oxidative DNA damage repair and relevance to human pathology.
Since DNA is prone to oxidative attack cells have evolved multiple protective strategies to prevent the deleterious effects of DNA oxidation. Base excision repair is the major mechanism for repair of DNA base damage by reactive oxygen species but recent evidence indicate that nucleotide excision repair proteins, that are mutated in human syndromes, are involved too. The mechanisms of repair dealing with the direct oxidation of DNA will be reviewed taking as prototype the oxidized base 7,8-dihydro-8-hydroxyguanine. The function of the individual repair components as inferred from model mice indicate that the ablation of two gene functions is mostly required to lead to accumulation of oxidative DNA damage, mutagenesis and cancer development. The recent identification of human diseases associated with mutations in oxidative damage repair show that defects in this pathway may lead to increased cancer but their major causative role seems to be in neurological diseases.
D'Errico
Mariarosaria
M
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Parlanti
Eleonora
E
Dogliotti
Eugenia
E
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species
C453560:7,8-dihydro-8-oxoguanine; D017382:Reactive Oxygen Species; D006147:Guanine