Disease relevance of ADE2

• The S. cerevisiae ADE2, HIS3 and URA3 genes were used with nutritional selections and the E. coli LacZ gene was used to quantitate reporter gene activation [1].
• A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans [2].
• HinfI hypersensitivity within the his3 promoter region is locally determined, since it was observed when this region was translocated to the middle of the ade2 structural gene [3].

High impact information on ADE2

• In diploid strains homozygous for an ochre mutation in ade2, cells carrying no copies of the SUP11 gene are red, those carrying one copy are pink, and those carrying two or more copies are white [4].
• The act3 his4delta-ADE2 colonies display both white and red sectors, showing that the two different phenotypes are possible in a single colony [5].
• The vacuole of the yeast Saccharomyces cerevisiae was visualized with three unrelated fluorescent dyes: FITC-dextran, quinacrine, and an endogenous fluorophore produced in ade2 yeast [6].
• In ade2 yeast, the bud usually inherits a substantial portion of its vacuole contents from the mother cell [6].
• Quinacrine, which diffuses across membranes and accumulates in acidic compartments in mammalian cells, can also be used as a marker for yeast vacuoles. ade2 yeast accumulate an endogenous fluorophore in their vacuoles [6].

Biological context of ADE2

• Two mcm10 mutants drastically reduce silencing of both URA3 and ADE2 reporter genes integrated into these silent loci [7].
• The C. albicans ADE2 gene was ligated into plasmid pRC2312 and the construct transformed Ade- strains of both C. albicans and S. cerevisiae to Ade+ [8].
• ADE2 was localized at chromosome V [9].
• Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination [10].
• We show here that these elements play a crucial role in ADE2 regulation since mutations in two such elements drastically reduced gene expression [11].

Anatomical context of ADE2

• However, their growth is considerably slowed down specially in non-acidic conditions; they are cold sensitive and thermo-sensitive, exhibit poor growth on glycerol medium, and do not accumulate in their vacuole the red pigment of ade2 strains [12].
• Spheroplast fusion and segregation experiments showed that the ADE2 genes on both the large and small chromosomes of C. stellatoidea are active, implying that the organism is functionally at least triploid for this gene and probably for any others duplicated on the smaller chromosomes [13].
• The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid [2].
• The sta2 gene, conferring the ability to metabolize starch was transferred from an auxotrophic haploid strain of S. cerevisiae (S. diastaticus) and the melibiose-metabolism (mel) gene(s), from S. kluyveri, to the kar1-1 mutant [K5-5A; (alpha ade2 his4 can1 gal) by normal mating and protoplast fusion [14].

Associations of ADE2 with chemical compounds

• As test cases, the chromosomal loci of the C. glabrata genes encoding aminoimidazole ribonucleotide carboxylase (ADE2) and encoding isopropylmalate dehydrogenase (LEU2) were deleted [15].
• The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes) [10].
• The promoters of the ADE2 gene, and of other genes involved in adenine biosynthesis, contain the hexanucleotide sequence TGACTC [11].
• The rad2 mutation affects the molecular nature of UV and acridine-mustard-induced mutations in the ADE2 gene of Saccharomyces cerevisiae [16].
• Our experiments indicate that the ADE2 gene of the purine biosynthetic pathway is under both specific adenine control and the general amino-acid control system [17].

Physical interactions of ADE2

• The factor BAS1 has been shown to bind at a site containing the TGACTC hexanucleotide motif in the ADE2 and ADE5,7 promoters [18].

Regulatory relationships of ADE2

• Unmasking of all the markers on chromosome VII leads to colonies that are white because ade3 sets a block preceding the ade2 block (which causes the accumulation of a precursor of the red pigment), they require leucine, tryptophan and methionine, and grow on media with cycloheximide [19].
• We have studied the molecular nature of ade2 mutations induced by UV light and bifunctional acridine-mustard (BAM) in wild-type (RAD) and in excision-deficient (rad2) strains of the yeast, Saccharomyces cerevisiae [16].

Other interactions of ADE2

• The cDNA that complemented ade2 (phosphoribosylaminoimidazole carboxylase) also complemented ade1 (phosphoribosylaminoimidazole succinocarboxamide synthetase), supporting earlier data suggesting that in some organisms these functions are part of a bifunctional protein [20].
• Clones were isolated that complement mutations in the yeast ADE2, ADE3, and ADE8 genes [20].
• This motif is required for both basal and induced activation of the ADE2 gene by BAS1 and BAS2 [18].
• The cloned C. albicans URA3 gene was disrupted with the C. albicans ADE2 gene, and the linearized DNA was used for transformation of two ade2 mutants, SGY-129 and A81-Pu [21].
• 7. PMA1 expression parallels expression of the constitutive ADE2 gene, increasing up to sixfold during yeast growth and twofold during germ tube formation [22].

Analytical, diagnostic and therapeutic context of ADE2

• Sequence analysis of the ADE2 gene coding for phosphoribosylaminoimidazole carboxylase in Schwanniomyces occidentalis [23].
• Molecular cloning and sequence analysis of Zygosaccharomyces rouxii ADE2 gene encoding a phosphoribosyl-aminoimidazole carboxylase [24].
• Sequence alignment of the phosphoribosylaminoimidazole carboxylase heterodimer from B. subtilis with the monomeric enzyme from Methanobrevibacter smithii indicates an evolutionary relationship between these two enzymes [25].
• Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented by the cryptococcal phosphoribosylaminoimidazole carboxylase gene (ade2) with a biolistic DNA delivery system [26].

References