Response of S. cerevisiae to N-methyl-N′-nitro-N-nitrosoguanidine: mutagenesis, survival and DDR gene expression
- 1 July 1985
- journal article
- research article
- Published by Springer Nature in Molecular Genetics and Genomics
- Vol. 200 (2) , 313-321
- https://doi.org/10.1007/BF00425442
Abstract
Summary We have examined the effects of low concentrations of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on survival and mutagenesis of logarithmically growing Saccharomyces cerevisiae. Pretreatment of cells with nontoxic and submutagenic concentrations of MNNG for several generations does not reduce the cytotoxic and mutagenic effects of exposure to a high concentration of drug. This lack of ‘adaptation’ in S. cerevisiae was further investigated biochemically and cell extracts prepared from pretreated cells were shown to be deficient in the ability to remove O6-methyl guanine from alkylated DNA. Moreover, we could not detect transfer of the methyl group from the DNA to a protein acceptor in yeast cell extracts suggesting that the level of O6-methyl guanine transferase is below 200 molecules/cell following pretreatment. Exposure of S. cerevisiae to mutagenic concentrations of MNNG stimulates transcription of at least three DNA damage responsive genes that also respond to UV-irradiation and 4-nitroquinoline-1-oxide treatment. These results support the contention that in Saccharomyces alkylation damage is processed by repair pathways that operate on a variety of lesions, and that one or more of these pathways is inducible.Keywords
This publication has 57 references indexed in Scilit:
- Lack of induction of O6-methylguanine-DNA methyltransferase in mammalian cells treated with N-methyl-N' -nitro-N-nitrosoguanidineCarcinogenesis: Integrative Cancer Research, 1984
- Adaptive response to simple alkylating agents in Bacillus subtilis cellsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1983
- An adaptive response to the cytotoxic effects of N-methyl-N-nitrosourea is apparently absent in normal human fibroblastsBiochimie, 1982
- Abilities of extracts of human lymphocytes to remove O6-methylguanine from DNAMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1982
- Adaptation to alkylation resistance involves the induction of a DNA glycosylaseNature, 1982
- Induction of a DNA glycosylase for N-methylated purines is part of the adaptive response to alkylating agentsNature, 1982
- Effect of pretreatment of rats with N-methyl-N-nitrosourea on the repair of O6-methylguanine in liver DNACarcinogenesis: Integrative Cancer Research, 1981
- Demethylation of O6-methylguanine in a synthetic DNA polymer by an inducible activity in EscherichiacoliBiochemical and Biophysical Research Communications, 1980
- Further studies on the induction of mutation in Haemophilus influenzae by N-methyl-N′-nitro-N-nitrosoguanidine: Lack of an inducible error-free repair system and the effect of exposure mediumMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1980
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976