Genetic control of the bypass of mono-adducts and of the repair of cross-links photoinduced by 8-methoxypsoralen in yeast.
A large UVA dose by itself induces lethal damage revealed in some repair-deficient strains of Saccharomyces cerevisiae. Following photoaddition of a monofunctional psoralen derivative, 3-carbethoxypsoralen, an extra killing effect is observed by applying a second high UVA dose, in conditions where a fraction of 8-methoxypsoralen (8-MOP) plus UVA-induced monoadducts are transformed into DNA cross-links. In an excision-repair-deficient context, the bypass of 8-MOP plus UVA-induced monoadducts is under the control of the RAD6+ gene product. However, when other steps of the mutagenic pathway are blocked by the rad18-2 or the pso1-1 mutations, bypass occurs. This is also true when in excision-deficient strains the recombinogenic pathway is blocked by the rad52-1 mutation. The recombinogenic pathway may be an alternative to the mutagenic pathway for bypass of monoadducts. The repair of the lesions induced by a second UVA dose applied after a first treatment by 8-MOP plus UVA [i.e. cross-links and other putative lesion(s)] is controlled by at least the RAD2+, RAD6+, RAD52+, PSO2+ and PSO1+ gene products. The role of the pathways involved is discussed according to the nature of the secondarily induced lesions.
D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004271:DNA, Fungal / Q000096:biosynthesis / Q000528:radiation effects; D005800:Genes, Fungal; D005838:Genotype; D008730:Methoxsalen / Q000378:metabolism / Q000494:pharmacology*; D010777:Photochemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D008730:Methoxsalen