Because of its relationship to aging and carcinogenesis, UV radiation mutagenesis has been an area of long-standing interest. Point mutations comprise the vast majority of UV radiation-induced mutations, whether in bacteria, fungi, viruses or mammalian cells. Caenorhabditis elegans apparently violates this dogma, as preliminary data indicate that most UV radiation-induced mutations in this free-living nematode are deficiencies. The purpose of this study is to understand why C. elegans misrepairs UV radiation-induced photoproducts into deficiencies rather than point mutations. To do so, mutation frequencies will be determined after UV irradiation in both germ lines. Pairs of such dose-response curves will be generated in DNA repair-proficient as well as three DNA repair-deficient genetic backgrounds. The mutations will be subjected to genetical and molecular tests designed to detect and analyze the size as well as location of deficiencies. Nucleotide sequences will be determined for selected mutations. It is anticipated that both the mutational frequencies and spectra (e.g., the ratio of point mutations versus deficiencies; size of deficiencies) will be germ-line and DNA repair dependent. Such differences will allow determination of the causative photoproduct(s) and repair processes which effect the misrepair of photoproducts into deficiencies.
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|Hartman, P; Childress, E; Beyer, T (1995) Nematode development is inhibited by methyl viologen and high oxygen concentrations at a rate inversely proportional to life span. J Gerontol A Biol Sci Med Sci 50:B322-6|