Mutat. Res.

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.

Source:http://purl.uniprot.org/citations/7520996