RAPID CHANGES OF NUCLEOTIDE EXCISION-REPAIR GENE-EXPRESSION FOLLOWINGUV-IRRADIATION AND CISPLATIN TREATMENT OF DICTYOSTELIUM-DISCOIDEUM

Organisms use different mechanisms to detect and repair different type s of DNA damage, and different species vary in their sensitivity to DN A damaging agents. The cellular slime mold Dictyostelium discoideum ha s long been recognized for its unusual resistance to UV and ionizing r adiation. We have recently cloned three nucleotide excision repair (NE R) genes from Dictyostelium, the repB, D and E genes (the homologs of the human xeroderma pigmentosum group B, D and E genes, respectively). Each of these genes has a unique pattern of expression during the mul ticellular development of this organism. We have now examined the resp onse of these genes to DNA damage. The repB and D DNA helicase genes a re rapidly and transiently induced in a dose dependent manner followin g exposure to both UV-light and the widely used chemotherapeutic agent cisplatin, Interestingly, the repE mRNA level is repressed by UV but not by cisplatin, implying unique signal transduction pathways for rec ognizing and repairing different types of damage. Cells from all stage s of growth and development display the same pattern of NER gene expre ssion following exposure to UV-light, These results suggest that the r esponse to UV is independent of DNA replication, and that all the fact ors necessary for rapid transcription of these NER genes are either st able throughout development, or are continuously synthesized. It is si gnificant that the up-regulation of the repB and D genes in response t o UV and chemical damage has not been observed to occur in cells from other species, We suggest that this rapid expression of NER genes is a t least in part responsible for the unusual resistance of Dictyosteliu m to DNA damage.