1887

Abstract

Various chemicals with harmful effects are not themselves toxic, but are metabolized to produce toxic products. One example is methanol in , which is lethal to cells containing the gene, but relatively harmless to mutants. This makes methanol resistance one of the tightest genetic selections in . Loss of also confers cross-resistance to unrelated compounds such as acriflavine and thiabendazole. We have used insertional mutagenesis to demonstrate that the locus encodes the peroxisomal catalase A enzyme. Disruption of the gene results in parallel resistance to acriflavine. Molecular and biochemical studies of several previously characterized methanol-resistant strains reveal that each lacks catalase activity. One allele, , contains a 13 bp deletion which introduces a frameshift in the middle of the gene. The involvement of catalase in methanol resistance in compares with its role in methanol metabolism in yeast and rodents. However, this is the first study to show that catalase is required for the toxicity of acriflavine. Our results imply that acriflavine and thiabendazole are precursors which must be oxidized to generate biologically active species. The gene is also a potentially invaluable negative selectable marker for molecular genetics.

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2002-01-01
2019-12-14
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