Yeast lacking superoxide dismutase. Isolation of genetic suppressors.

X.F Liu,I Elashvili,E.B Gralla,J.S Valentine,P Lapinskas,V.C Culotta

doi:10.1016/s0021-9258(19)36959-5

X.F Liu, I Elashvili + Show 4 more

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https://doi.org/10.1016/s0021-9258(19)36959-5

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Abstract

Null mutants of superoxide dismutase (SOD) in Saccharomyces cerevisiae are associated with a number of biochemical defects. In addition to being hypersensitive to oxygen toxicity, strains containing deletions in both the SOD1 (encoding Cu/Zn-SOD) and SOD2 (encoding Mn-SOD) genes are defective in sporulation, are associated with a high mutation rate, and are unable to biosynthesize lysine and methionine. The sod-linked defect in lysine metabolism was explored in detail and was found to occur at an early step in lysine biosynthesis, evidently at the level of the alpha-amino adipate transaminase. To better understand the role of SOD in cell metabolism, our laboratory has isolated yeast suppressors that have bypassed the SOD defect ("bsd" strains), that is, S. cerevisiae cells lacking SOD, yet resistant to oxygen toxicity. Two nuclear bsd complementation groups have been identified, and both suppress a variety of biological defects associated with sod1 and sod2 null mutants. These results demonstrate that a single gene mutation can alleviate the requirement for SOD in cell growth. Both bsd complementation groups are unable to utilize many non-fermentable carbon sources, suggesting a possible suppressor-linked defect in electron transport.

Highlights

From the $Division of Toxicological Sciences, Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 22205 and the §Department of Chemistry and Biochemistry, University of California, Los Angeles, Calfornia 90024
Null mutants of superoxide dismutase (SODin) Suc- oxygen toxicity involves one or another form of the enzyme charomyces cereuisiae are associated with a number superoxide dismutase (SOD).’In eukaryotes, SOD exists both of biochemical defects
Direct evidence for the in both the SOD1and SOD2 protective role of SOD against oxygen toxicity has emerged enes are defective in sporulation, are associated with a high mutationrate, and are unable to biosynthesize lysine and methionine

Summary

ISOLATION OF GENETIC SUPPRESSORS*

Vol 267, No 26, Issue of September 15, pp. 18298-18302,1992 Printed in U.S.A. Xiu Fen LiuSI,lya ElashviliS, Edith ButleGr rallaj, Joan SelverstoneValentine#, PaulaLapinskasSTi, and Valeria CizewskCi ulottaSII. Null mutants of superoxide dismutase (SODin) Suc- oxygen toxicity involves one or another form of the enzyme charomyces cereuisiae are associated with a number superoxide dismutase (SOD).’In eukaryotes, SOD exists both of biochemical defects. In addition to being hypersen- as a manganese-containing enzyme located in themitochonsitive to oxygen toxicity, strains containing deletions dria and as a cytosolic Cu/Zn-SOD. (“bsd”strains), that is, S. cereuisiue cells lacking SOD, In addition to oxygen sensitivity, several metabolic defects yet resistant tooxygen toxicity. In S. cerement for SOD in cell growth Both bad complementa- ukiae, sodl strains lacking a functional Cu/Zn-SOD are notion groupsare unable toutilize many non-fermentable tably defective in sulfur metabolism and are auxotrophic for carbonsources, suggesting apossiblesuppressorlysine and methionine when grown aerobically [13,14,15,16,17]. With prokaryotes, eukaryotic SOD may act toprotect numerous metabolic enzymes against oxygen-induced damage

The research presented here represents a genetic approach

AND DISCUSSION

Sporulation efficiencies of heterozygousand homozygous soda diploids

MATa haploids