Neurospora mutants affecting polyamine-dependent processes and basic amino acid transport mutants resistant to the polyamine inhibitor, alpha-difluoromethylornithine.
Polyamines (spermidine and spermine) are required by living cells, but their functions are poorly understood. Mutants of Neurospora crassa with enhanced or diminished sensitivity to interference with polyamine synthesis, originally selected to study the regulation of the pathway, were found to have unexpected defects. A group of four non-allelic mutations, causing no interference with polyamine synthesis, each imparted spermidine auxotrophy to a genotype already partially impaired in spermidine synthesis. Strains carrying only the new mutations displayed unconditional delay or weakness at the onset of growth, but grew well thereafter and had a normal or overly active polyamine pathway. These mutants may have defects in vital macromolecular activities that are especially dependent upon the polyamines-activities that have not been identified with certainty in studies to date. Another group of mutants, selected as resistant to the polyamine inhibitor difluoromethylornithine (DFMO), had normal activity and regulation of ornithine decarboxylase, the target of the drug. All but one of thirty mutants were allelic, and were specifically deficient in the basic amino acid permease. This mechanism of DFMO resistance is unprecedented among the many DFMO-resistant cell types of other organisms and demonstrates that DFMO can be used for efficient genetic studies of this transport locus in N. crassa.
Davis
R H
RH
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Lieu
P
P
Ristow
J L
JL
D000596:Amino Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D004352:Drug Resistance, Microbial; D000518:Eflornithine / Q000494:pharmacology*; D009154:Mutation; D009492:Neurospora crassa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D011073:Polyamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012641:Selection, Genetic
D000596:Amino Acids; D011073:Polyamines; D009955:Ornithine Decarboxylase; D000518:Eflornithine