PSORALEN DAMAGE--INDUCED REPAIR AND RECOMBINATION

Psoralen is a photoreactive compound which produces covalent adducts and interstrand crosslinks in DNA. Treatment with psoralen plus near UV light induces genotoxic effects such as mutations, recombination and chromosomal aberrations in many organisms, and produces skin cancer in humans and rodents. The repair and genotoxic effects of psoralen DNA damage will be studied in the yeast Saccharomyces cerevisiae, a lower eukaryote with genetically well-characterized DNA repair systems. Plasmid DNA molecules containing site-specifically placed psoralen monoadducts or crosslinks will be prepared in vitro and introduced into yeast cells. Repair will be measured in repair-proficient or repair- deficient strains. The frequency of recombination between the damaged plasmids and homologous chromosomal sequences will be measured in different genetic backgrounds. The recombinants will be analyzed for gene conversion and reciprocal exchange. Multiple recombination events and chromosomal translocations will also be studied.