Fate of photo-induced 8-methoxypsoralen mono-adducts in yeast. Evidence for bypass of these lesions in the absence of excision repair.
A fraction of UVA-induced 8-methoxypsoralen (8-MOP) mono-adducts can be transformed by a second UVA (365 nm) irradiation procedure into lethal cross-links in Saccharomyces cerevisiae. To follow the fate of cross-linkable mono-adducts, cells were incubated in complete medium between the two UVA doses and survival was measured. The killing effect of the second UVA dose decreases rapidly in haploid wild-type as well as in strains blocked in mutagenic (RAD6+ type) or in recombinogenic (RAD52+ type) repair pathways. This is also true in the pso1-1 and pso2-1 strains selected for sensitivity to 8-MOP plus UVA treatment. In contrast, persistence of mono-adducts is observed in strains blocked in the excision-resynthesis repair pathway. In other words, cross-linkable mono-adducts are repaired by the excision process. The use of the cell-cycle conditional mutant strain (cdc14-1) permitted us to apply the second dose at a specific cell-cycle stage (post-G2 phase) after a 'priming' UVA treatment on stationary (G1) phase cells. Such experiments showed a bypass of mono-adducts in an excision-deficient context for at least one round of DNA replication.
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005804:Genes, Lethal; D005838:Genotype; D007700:Kinetics; D008730:Methoxsalen / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D013045:Species Specificity; D014466:Ultraviolet Rays
D008730:Methoxsalen