DNA PHOTODAMAGE, REPAIR, GENE INDUCTION AND GENOTOXICITY FOLLOWING EXPOSURES TO 254 NM UV AND 8-METHOXYPSORALEN PLUS UVA IN A EUKARYOTIC CELL SYSTEM

The induction and repair of different types of photodamage and photoge notoxicity in eukaryotic cells have been the subject of many studies. Little is known about possible links between these phenomena and the i nduction of DNA damage-inducible genes. We explored this relationship using the yeast Saccharomyces cerevisiae, a pertinent eukaryotic model . Previous results showed that the photogenotoxic potential of 8-metho xypsoralen (8-MOP) plus WA is higher than that of UV (254 nm), Moreove r, the induction of the ribonucleotide reductase gene RNR2 by UV and 8 -MOP plus UVA in an RNR2-LACZ fusion strain and the formation of DNA d ouble-strand breaks (dsb) as repair intermediates after such treatment s suggest that the latter process could involve a signal for gene indu ction. To further substantiate this, we measured the induction of the DNA repair gene RAD51 in RAD51-LACZ fusion strains using the dsb repai r and recombination deficient mutant rad52 and the corresponding wild type, and we determined the formation of dsb by pulsed-field gel elect rophoresis. After treatments, the resealing of dsb formed as repair in termediates was impaired in the rad52 mutant, At equal doses, i,e, the same number of lesions, the induction of the RAD51 gene by UV or 8-MO P plus UVA was significantly reduced in the rad52 mutant as compared w ith the wild type. The same was true when equitoxic doses were used. T hus, the RAD52 repair pathway appears to play an important role not on ly in dsb repair but also in gene induction. Furthermore, the signalin g pathways initiated by DNA damage and its processing are somewhat lin ked to the photogenotoxic response.