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 w ith 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 mu tations, causing no interference with polyamine synthesis, each impart ed spermidine auxotrophy to a genotype already partially impaired in s permidine 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 mutant s, selected as resistant to the polyamine inhibitor difluoromethylorni thine (DFMO), had normal activity and regulation of ornithine decarbox ylase, the target of the drug. All but one of thirty mutants were alle lic, and were specifically deficient in the basic amino acid permease. This mechanism of DFMO resistance is unprecedented among the many DFM O-resistant cell types of other organisms and demonstrates that DFMO c an be used for efficient genetic studies of this transport locus in N. crassa.