title: Sensitivity to nitrogen mustard in Saccharomyces cerevisiae is independently determined by regulated choline permease and DNA repair.
abstract: Sensitivity of yeast cells to the bifunctional alkylating agent nitrogen mustard (HN2) depends on two independently operating physiological mechanisms of cellular metabolism: dynamics of uptake of HN2 via choline permease, encoded in the gene HNM1/CTR, and repair of HN2-induced DNA damage. Uptake of choline and HN2 is impaired in mutant alleles of HNM1/CTR, leading to a HN2 hyper-resistant phenotype. Overexpression of HNM1/CTR leads to HN2 sensitivity higher than that of the wild type. While mutation and regulation of HNM1/CTR have pronounced effects on the cell's HN2 sensitivity, they do not interfere with repair of HN2-induced DNA damage, a process whose quality independently determines a yeast cell's sensitivity to HN2. Consequently, HNM1/CTR overexpression in an excision repair-deficient strain leads to extreme HN2 sensitivity whereas a mutational block of HNM1/CTR, in combination with excision proficiency, yields a HN2 hyper-resistant phenotype.
authors.affiliation: Institut für Mikrobiologie der J.W. Goethe-Universität, Frankfurt/Main, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Brendel
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D004271:DNA, Fungal / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D007294:Inositol / Q000378:metabolism; D008466:Mechlorethamine / Q000378:metabolism / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D009154:Mutation / Q000502:physiology; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; C065637:choline transporter; D007294:Inositol; D008466:Mechlorethamine; D002794:Choline