The effect of genes controlling radiation sensitivity on chemical mutagenesis in yeast.

Abstract

A special set of mutants containing identified altered codons in the iso-1-cytochrome c gene of yeast were recently used as tester strains for determining mutagenic specificities (Prakash and Sherman, 1973). One of the mutants, cyc1–131, contains a GUG codon in place of the normal chain-initiation codon AUG and requires a G•C-to-A•T transition to yield the normal protein (Stewart et al., 1971). This mutant was reverted preferentially and with a high frequency by ethyl methanesulfonate (EMS), diethyl sulfate (DES), nitrous acid (HNO2), N-methyl-N ′-nitro-N-nitrosoguanidine (NTG), nitrosoimidazolidone (NIL), [3H] uridine ([3H] U), nitroquinoline oxide (NQO), and β-propioloactone (β-PL), and it was therefore concluded that these agents selectively induced G•C-to-A•T transitions (Prakash and Sherman, 1973; Prakash et al., 1974). In addition, ultraviolet light (UV), X-rays, nitrogen mustard (HN2), methyl methanesulfonate (MMS), and dimethyl sulfate (DMS) were found to revert all the tester strains with the same efficiency or without any dependence on simple types of base-pair changes, and it was concluded that these mutagens were nonspecific in the types of base-pair changes produced. Since the cyc1–131 tester reverted well with all 11 chemical mutagens and with ionizing and UV radiation, it was used in studies designed to determine the genetic control of mutation induction using a wide variety of mutagens (Prakash, unpublished results). This tester was coupled to over 20 different rad genes (the symbol for loci conferring radiation sensitivity in yeast), and diploids were constructed which were homozygous for cyc1–131 as well as a particular rad gene.