The clinical drug psoralen, used to treat patients with pigmentation disorders, has been shown to cause formation of cross-links between DNA strands. Other known DNA cross-linking agents are commonly used in cancer chemotherapy. However, these antineoplastic agents produce DNA defects which are not chemically stable and the induced DNA damages are rather non-specific. Taking advantage of the high degree of specificity of formation and the known stability of the psoralen cross- linking defect in DNA, molecular mechanisms involved in the cellular repair of cross-links in E. coli and mouse L5178Y leukemia-lymphoma cells in tissue culture will be studied. The genetic recombination and excision-repair functions are known to complement one another in repairing cross-linking damages. Intermediates and products of these repair processes will be labeled with radioactive and density isotopes, isolated by ultracentrifugation and column chromatography techniques, and characterized biochemically and by electron microscopy. Whether cross-links pass through the growth fork during replication will be established. The chemistry and photobiology of the psoralen reaction with DNA will be studied. Rates of the photochemical binding to synthetic polynucleotides will be measured in order to establish which specific DNA sequences psoralen preferentially binds to. The chemical structure of the psoralen cross-linking adduct to DNA will also be established.