Balzi E, Chen W, Ulaszewski S, Capieaux E, Goffeau A
Laboratoire d'Enzymologie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
J Biol Chem. 1987 Dec 15;262(35):16871-9.
The Saccharomyces cerevisiae gene PDR1, responsible for pleiotropic drug resistance, was isolated from a genomic DNA cosmid library by hybridization to the flanking LEU1 gene, followed by subcloning the drug-sensitive phenotype into the transformed pdr1-1, pdr1-2, and pdr1-3 drug-resistant mutants. A RNA molecule of 3.5 kilobases was identified as the PDR1 transcript. The nucleotide sequence of the complementing DNA fragment contained a 3192-nucleotide open reading frame. Disruption of the pdr1 and PDR1 genes restored or increased drug sensitivity. Analysis of the PDR1 deduced amino acid sequence revealed several homologies to four different regulatory proteins involved in the control of gene expression, including a cysteine-rich motif suggested to be a metal-binding domain for DNA recognition. A model is proposed of a general transcriptional control by PDR1 of several target genes encoding proteins from plasma, mitochondria, and possibly other permeability barriers.
负责多药耐药性的酿酒酵母基因PDR1，是通过与侧翼的LEU1基因杂交，从基因组DNA黏粒文库中分离出来的，随后将药物敏感表型亚克隆到转化的pdr1-1、pdr1-2和pdr1-3耐药突变体中。一个3.5千碱基的RNA分子被鉴定为PDR1转录本。互补DNA片段的核苷酸序列包含一个3192个核苷酸的开放阅读框。pdr1和PDR1基因的破坏恢复或增加了药物敏感性。对PDR1推导的氨基酸序列分析显示，它与参与基因表达调控的四种不同调节蛋白有几个同源性，包括一个富含半胱氨酸的基序，该基序被认为是用于DNA识别的金属结合域。提出了一个模型，即PDR1对几个编码来自质膜、线粒体以及可能其他通透性屏障的蛋白质的靶基因进行一般转录调控。
