Disease relevance of ADE3

• These results are also consistent with those obtained in heterologous expression of spinach and Clostridium acidiurici monofunctional synthetases in ade3 strains [1].

High impact information on ADE3

• This hypothesis is based on their finding that the presence of the full-length ADE3 C1-THF synthase, whether catalytically active or not, is correlated with the Ade+ phenotype [1].
• In contrast to their results, our deletion analysis of the ADE3 gene indicates that the presence of either the synthetase or dehydrogenase/cyclohydrolase domains of C1-THF synthase is enough to complement the adenine requirement in ade3 strains [1].
• Clones were isolated that complement mutations in the yeast ADE2, ADE3, and ADE8 genes [2].
• RSR1 maps between CDC62 and ADE3 on the right arm of chromosome VII; its predicted product is approximately 50% identical to other proteins in the ras family [3].
• Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements [4].

Chemical compound and disease context of ADE3

• Heterologous expression of the Clostridium acidiurici gene encoding a monofunctional 10-formyl-THF synthetase in an ade3 deletion strain did not restore growth in the absence of adenine, even though the monofunctional synthetase was catalytically competent in vivo [5].
• The feasibility and versatility of the method is shown with the yeast ADE3 gene encoding the cytoplasmic C1-THF synthase and the gene encoding the monofunctional 10-formyl-THF synthetase from Clostridium acidiurici [6].

Biological context of ADE3

• Frequently, the plasmid carries the ADE3 gene and mutants are recognized as red colonies that fail to produce sectors [7].
• In addition, we report the identification of a truncated ADE3 allele with a unique coloration phenotype and show that it can be used to improve synthetic lethal screens [7].
• Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes [7].
• An unusual open reading frame that is encoded by a very unbiased set of codons follows the ADE3 gene [8].
• Nucleotide sequence of the Saccharomyces cerevisiae ADE3 gene encoding C1-tetrahydrofolate synthase [8].

Anatomical context of ADE3

• Inactivation of SHM1, SHM2 and ADE3 is required to render yeast auxotrophic for TMP and methionine, suggesting that TMP synthesized in mitochondria may be available to the cytoplasmic compartment [9].

Associations of ADE3 with chemical compounds

• Nonetheless, point mutants of Shm2p that were catalytically inactive (i.e. failed to rescue the methionine auxotrophy of a shm2Delta ade3 strain) complemented the synthetic lethal phenotype, thus revealing a novel metabolism-independent function of Shm2p [10].
• Shm2p and Ade3p are cytoplasmic enzymes producing 5,10-methylene tetrahydrofolate in convergent pathways as the primary source for cellular one-carbon groups [10].
• The effect of mutations in LPD1 (L-subunit of GDC), SER1 (synthesis of serine from 3-phosphoglycerate), ADE3 (cytoplasmic synthesis of one-carbon units for the serine synthesis from glycine), and all combinations of each has been determined [11].
• In the present work, site-directed mutagenesis of the S. cerevisiae ADE3 gene, which encodes C1-THF synthase, was used to individually change each cysteine contained within the dehydrogenase/cyclohydrolase domain (Cys-11, Cys-144, and Cys-257) to serine [12].
• This trifunctional enzyme, encoded by the ADE3 gene in the yeast Saccharomyces cerevisiae, is thought to be responsible for the synthesis of the one-carbon donor 10-formyl-THF for de novo purine synthesis [5].

Regulatory relationships of ADE3

• 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 [13].

Other interactions of ADE3

• The yeast BIO2 and ZUO1 genes reside near ADE3 gene on chromosome VII [14].
• The HIP1 gene maps to the right arm of chromosome VII, approx. 11 cM distal to the ADE3 gene [15].
• Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae [16].
• A plasmid containing the ADE3/ADE8 gene and the wild-type gene of interest must then be transformed into the strain, which results in red colonies with white sectors where the plasmid has been lost [17].
• In this work, we show that an ade16 ade17 double disruption also leads to histidine auxotrophy, similar to the adenine/histidine auxotrophy of ade3 mutant yeast strains [18].

Analytical, diagnostic and therapeutic context of ADE3

• Determination of the amount of C1-THF synthase mRNA under the various growth conditions by an in vitro translation/immunoprecipitation assay indicates that regulation of the enzyme occurs predominantly at a pretranslational level since steady-state levels of C1-THF synthase mRNA are 2-3-fold higher in derepressed cells than in repressed cells [19].

References