High impact information on LEU1

• We have cloned, mapped and sequenced the gene encoding the yeast plasma membrane ATPase (PMA1) and report here that it maps to chromosome VII adjacent to LEU1 [1].
• Although the majority of genes for amino acid biosynthesis which have been examined are under general amino acid control, LEU1 and LEU2 of Saccharomyces cerevisiae respond specifically to leucine [2].
• The lysine and leucine biosynthetic pathways each contain a 4Fe-4S cluster enzyme homologous to aconitase and likely to be superoxide-sensitive, homoaconitase (Lys4p) and isopropylmalate dehydratase (Leu1p), respectively [3].
• Located in the cytosol and intermembrane space of the mitochondria, Sod1p likely provides direct protection of the cytosolic enzyme Leu1p [3].
• 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 [4].

Biological context of LEU1

• It also has six blocks of homology in common with the 5' flanking regions of two other LEU structural genes (LEU1 and LEU2) [5].
• This phenotype was used to map the pma1 mutation adjacent to LEU1 gene on chromosome VII [6].
• Comparison of the regulatory region of C-LEU2 with those of LEU1 and LEU2 suggested a few short consensus sequences which are involved in regulation of gene expression by leucine and threonine in the medium [7].
• In yeast, coincident gene conversion events involving the LEU1 and TRP5 loci (16 cM apart) occur at frequencies that are far greater than is expected for two independent acts of recombination [8].
• We have examined this possibility in further detail by introducing, via transformation, a large plasmid insertion between the LEU1 and TRP5 loci and studying its behavior among coincident convertants involving the flanking sites [9].

Associations of LEU1 with chemical compounds

• Sequence analysis indicated that the MTC was integrated in the LEU1 locus in N083, a leucine-auxotrophic mutant, in the isocitrate dehydrogenase gene of N156 (alkE leaky), in the thioredoxin reductase gene in N040 (alkAc), and in a peroxine gene (PEX14) in N078 (alkD) [10].
• In the first group borrelidin resistance is coupled to the gene HOM3 coding for aspartokinase, in the second group to the gene LEU1 [11].
• Yeast alpha-isopropylmalate isomerase. Factors affecting stability and enzyme activity [12].
• Yeast alpha-isopropylmalate isomerase was found to be markedly stabilized by high concentrations of glycerol and (NH4)2SO4 [12].
• Neither isopropylmalate isomerase nor beta-isopropylmalate dehydrogenase responded to general control signals [13].

Physical interactions of LEU1

• During mitosis, gene conversion events at the TRP5 locus on chromosome VII are coupled with conversion events at LEU1, a locus 18 cM away, 1200 times more frequently than would be expected for two independent acts of recombination [14].

Other interactions of LEU1

• After recloning into an integrating vector, a subfragment (of the 3.5-kb fragment) directs a URA3 marker to integrate at the LEU1 locus [15].
• Although physical mapping suggests that MSB2 and LEU1 (on the left arm of chromosome VII) are approximately 40 kb apart, the genetic map distance observed between leu1 and an msb2::URA3 marker was only 2.3 cM [16].
• We found that the LEU1, LEU2, and BAT1 genes were up-regulated in TFL20 for metabolism, and that TFL20 simultaneously produced as much i-AmOH and leucine as K30 does [17].
• The metal involvement and some of the other properties of alpha-isopropylmalate isomerase reveal a similarity to aconitase [12].
• Growth in an acetate medium results in derepression of the first enzyme in the pathway, alpha-isopropylmalate synthase, and repression of the second two enzymes, alpha-isopropylmalate isomerase and beta-isopropylmalate dehydrogenase, relative to the levels found in glucose-grown cells [18].

Analytical, diagnostic and therapeutic context of LEU1

• Northern blots with a LEU1-specific probe showed the size of the LEU1 transcript (about 2.9 kb) is consistent with the size of the enzyme and steady state levels of the transcript are sharply reduced in cells grown in the presence of an elevated leucine concentration [15].
• The restriction map of the 5 kb HindIII fragment and Southern blot analysis reveal that the cloned fragment contains the entire structural gene for the plasma membrane ATPase and the 5' end of the adjacent LEU1 gene [6].

References