Repair and mutagenesis in lower eukaryotes: a summary and perspective.

Abstract

The impetus for the research reviewed in the session “Repair and Mutagenesis in Lower Eukaryotes” came in part from related research in Escherichia coli and other prokaryotes. Mutants that are more sensitive than wild type to the killing activity of a mutagen (mutagen-sensitive strains) were reported in Neurospora crassa and Saccharomyces cerevisiae in 1967-three years after the first reports of the enzymatic removal of thymine dimers from DNA (nucleotide excision repair) in E. coli by Setlow and Carrier and by Boyce and Howard-Flanders, two years after Clark and Margulies reported results with recombination-deficient mutants of E. coli that indicated an association between recombination and DNA repair, and in the same year that Witkin proposed that UV-induced DNA lesions in E. coli were repaired by mutation-proof and mutation-prone pathways. The early investigators of DNA repair in eukaryotes were interested in whether the repair mechanisms being elucidated in prokaryotes would occur in eukaryotes, and they also suspected that the mechanisms for repair would be more complex in eukaryotes than in prokaryotes. The lower eukaryotes S. cerevisiae and N. crassa became the objects of a great deal of the research on DNA repair in eukaryotes. It was thought that the increase in complexity of the DNA repair mechanisms would be less for the lower eukaryotes than for higher eukaryotes and, therefore, that these mechanisms would be somewhat simpler to elucidate in yeast and Neurospora than in higher eukaryotes. Both of these lower eukaryotes generally have the advantage of ease-of-handling of prokaryotic microbes, and there is a large body of literature on their genetics and biochemistry. Moreover, the structures in which radiation or chemicals cause lesions—and in which those lesions may be repaired—are eukaryotic chromosomes, which undergo mitosis and meiosis. Therefore, researchers on DNA repair in Neurospora and yeast thought that the mechanisms of repair they were elucidating might be applicable, at least in a general way, to higher eukaryotes, including humans.