Lecrenier N, Foury F
Unité de Biochimie Physiologique, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Mol Gen Genet. 1995 Nov 1;249(1):1-7. doi: 10.1007/BF00290229.
A multicopy suppressor gene which rescues the temperature-sensitive growth defect of Saccharomyces cerevisiae mutants in the mitochondrial DNA (mtDNA) polymerase-encoding MIP1 gene has been isolated and identified as the RNR1 gene. This gene, whose transcript is cell cycle-regulated and mainly expressed at the G1 to S phase transition, encodes the large subunit of ribonucleotide reductase. This enzyme catalyses a limiting step in the production of deoxynucleotides needed for DNA synthesis. The presence of a high copy number of the RNR1 gene also decreases the accumulation of rho- mutants observed in diploids that harbour a single copy of the MIP1 gene. In cell cycle-synchronised cells, the presence of a high copy number of RNR1 does not modify its cell cycle transcription regulation and increases its transcript level by a factor of 10 throughout the cell cycle. Our results show that an increased supply of dNTPs in mitochondria can stimulate the mtDNA polymerase activity and indicate that the dNTP concentration may be rate limiting for the replication of mtDNA.
一个多拷贝抑制基因已被分离并鉴定为RNR1基因，它能挽救线粒体DNA（mtDNA）聚合酶编码基因MIP1中酿酒酵母突变体的温度敏感生长缺陷。该基因的转录本受细胞周期调控，主要在G1到S期转换时表达，编码核糖核苷酸还原酶的大亚基。这种酶催化DNA合成所需脱氧核苷酸生产中的一个限速步骤。RNR1基因高拷贝数的存在还减少了在携带单拷贝MIP1基因的二倍体中观察到的rho-突变体的积累。在细胞周期同步化的细胞中，RNR1基因高拷贝数的存在不会改变其细胞周期转录调控，并且在整个细胞周期中将其转录水平提高10倍。我们的结果表明，线粒体中脱氧核苷酸三磷酸（dNTPs）供应的增加可以刺激mtDNA聚合酶活性，并表明dNTP浓度可能是mtDNA复制的限速因素。
