DNA Repair and Mutagenesis in Yeast

INTRODUCTION Physical and chemical mutagens can produce various kinds of structural defects in yeast DNA. Under appropriate vegetative growth conditions, such changes in DNA may lead to killing (measured as inhibition of macrocolony formation), mutation, or mitotic recombination. Sensitivity to these effects depends on the nature of the mutagen, on the genetic constitution of the cells, and on their physiological state before, during, and after exposure. For reviews of early work in this area see Mortimer (1961), Haynes (1964a, 1975a), James and Werner (1965), and Kilbey (1975). Our knowledge of the mechanisms of DNA repair and its involvement in mutagenesis has come primarily from genetic and biochemical studies on the effects of ultraviolet light (254 nm UV) on microorganisms, including yeast (Haynes et al. 1966; Hanawalt and Setlow 1975; Hanawalt et al. 1978, 1979). Therefore, in this chapter, our discussion of general concepts is based largely on experimental results from the UV photobiology of Saccharomyces cerevisiae. However, most of the ideas are applicable in broad outline, if not in precise genetic or biochemical detail, to the corresponding cellular responses to ionizing radiation and chemical mutagens. For information concerning these latter mutagens, as well as UV, see the recent articles by Kircher et al. (1979), Resnick (1979), Ruhland and Brendel (1979), Lemontt (1980), Prakash and Prakash (1980) and Lawrence (1981). At the observational level in large populations, the genetic effects of UV are randomly distributed, generally independent of one another, and the dose-response relations can be described formally by single-event1 Poisson...