Hyper-resistance to nitrogen mustard in Saccharomyces cerevisiae is caused by defective choline transport.
The recessive hnm1 mutant allele is responsible for hyper-resistance to nitrogen mustard in Saccharomyces cerevisiae. Transformation with a single-copy HNM1 wild-type allele of such hyper-resistant mutants will restore wild-type sensitivity to nitrogen mustard. By contrast the presence of multi-copy vectors containing HNM1, in either a hyper-resistant hnm1 mutant or an HNM1 wild-type, will lead to a novel, mustard-sensitive phenotype unrelated to defects in DNA repair genes. Gene disruption of HNM1 revealed that this gene is non-essential for cells prototrophic for choline (CHO1) but lethal for cells with a cho1 genotype. Sensitivity to nitrogen mustard of wild-type HNM1, but not of hnm1 mutants, depends on the choline content of the growth medium, with cells grown in choline-free medium exhibiting the highest sensitivity. Sequencing of a 300 bp DNA fragment of HNM1 revealed the identity of this gene with the CTR locus, which is responsible for choline transport in Saccharomyces cerevisiae.
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Institut für Mikrobiologie, J.W. Goethe-Universität, Frankfurt, Federal Republic of Germany.
Haase
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Brendel
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D000483:Alleles; D001692:Biological Transport / Q000187:drug effects; D002794:Choline / Q000378:metabolism*; D003001:Cloning, Molecular; D004249:DNA Damage; D004352:Drug Resistance, Microbial; D005800:Genes, Fungal / Q000187:drug effects; D008466:Mechlorethamine / Q000494:pharmacology*; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*
D008466:Mechlorethamine; D002794:Choline