Kern L, de Montigny J, Lacroute F, Jund R
Laboratoire de Génétique Physiologique, Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
Curr Genet. 1991 May;19(5):333-7. doi: 10.1007/BF00309592.
In Saccharomyces cerevisiae, the protein encoded by the FUR1 gene is absolutely required for the expression of uracil phosphoribosyl transferase activity. The occurrence of semi-dominant mutations for 5-fluorouracil-(5FU)-resistance at this locus led us to clone and sequence the semi-dominant fur1-5 allele. A single point mutation, resulting in the substitution of arginine 134 for serine, is responsible for this mutant phenotype. The fur1-5 allele is transcribed and expressed at the same level as the wild-type allele. But, in contrast with the wild-type, the UPRTase activity of the fur1-5 mutant strain is stimulated in vitro by UTP and does not, therefore, correspond to a loss of feedback of UPRTase activity. We found that uracil, as a free base, induces a significative increase in transcription and UPRTase activity in a wild-type strain as well as in uracil-overproducing mutants which principally explains the high efficiency of the pyrimidine salvage pathway in S. cerevisiae.
在酿酒酵母中，FUR1基因编码的蛋白质是尿嘧啶磷酸核糖基转移酶活性表达所绝对必需的。该位点出现的对5-氟尿嘧啶（5FU）具有抗性的半显性突变促使我们克隆并测序半显性fur1-5等位基因。一个单点突变导致第134位精氨酸被丝氨酸取代，正是这个突变导致了该突变表型。fur1-5等位基因的转录和表达水平与野生型等位基因相同。但是，与野生型不同的是，fur1-5突变株的UPRTase活性在体外受到UTP的刺激，因此，这并不对应于UPRTase活性反馈的丧失。我们发现，作为游离碱的尿嘧啶会导致野生型菌株以及尿嘧啶过量产生突变体中转录和UPRTase活性显著增加，这主要解释了酿酒酵母中嘧啶补救途径的高效性。
