UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae.
UVA (320-400 nm) radiation constitutes >90% of the environmentally relevant solar UV radiation, and it has been proposed to have a role in skin cancer and aging. Because of the popularity of UVA tanning beds and prolonged periods of sunbathing, the potential deleterious effect of UVA has emerged as a source of concern for public health. Although generally accepted, the impact of DNA damage on the cytotoxic, mutagenic, and carcinogenic effect of UVA radiation remains unclear. In the present study, we investigated the sensitivity of a panel of yeast mutants affected in the processing of DNA damage to the lethal and mutagenic effect of UVA radiation. The data show that none of the major DNA repair pathways, such as base excision repair, nucleotide excision repair, homologous recombination, and postreplication repair, efficiently protect yeast from the lethal action of UVA radiation. In contrast, the results show that the Ogg1 DNA glycosylase efficiently prevents UVA-induced mutagenesis, suggesting the formation of oxidized guanine residues. Furthermore, sequence analysis of UVA-induced canavanine-resistant mutations reveals a bias in favor of GC-->TA events when compared with spontaneous or H(2)O(2)-, UVC-, and gamma-ray- induced canavanine-resistant mutations in the WT strain. Taken together, our data point out a major role of oxidative DNA damage, mostly 7,8-dihydro-8-oxoguanine, in the genotoxicity of UVA radiation in the yeast Saccharomyces cerevisiae. Therefore, the capacity of skin cells to repair 7,8-dihydro-8-oxoguanine may be a key parameter in the mutagenic and carcinogenic effect of UVA radiation in humans.
Kozmin
S
S
Institut Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 2027, Bâtiment 110, Centre Universitaire, 91405 Orsay Cedex, France.
Slezak
G
G
Reynaud-Angelin
A
A
Elie
C
C
de Rycke
Y
Y
Boiteux
S
S
Sage
E
E
D000375:Aging / Q000187:drug effects / Q000528:radiation effects; D002172:Canavanine / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D009154:Mutation / Q000187:drug effects / Q000528:radiation effects; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000201:enzymology; D012878:Skin Neoplasms / Q000201:enzymology / Q000209:etiology; D014466:Ultraviolet Rays / Q000009:adverse effects
C453560:7,8-dihydro-8-oxoguanine; D029701:Saccharomyces cerevisiae Proteins; D002172:Canavanine; D006147:Guanine; D045647:DNA Glycosylases; C505160:Ogg1 protein, S cerevisiae