Disease relevance of URA1

• Comparisons between the amino acid sequence of the yeast DHOdehase and sequences of DHOdehases previously isolated from Dictyostellum discoïdum, Escherichia coli and Bacillus subtilis reveal no obvious homologies [1].
• The absence of URA1 expression in E. coli can be corrected by the spontaneous integration into the cloned yeast DNA of a 0.9-kb bacterial DNA [2].
• The URA1 gene (encoding orotidine-5'-monophosphate decarboxylase) of the basidiomycete fungus Schizophyllum commune was mapped to a 1.4-kb BglI-BamHI fragment of two independent phage lambda clones previously isolated from a Schizophyllum genomic library [3].
• In the characterization of the pyrimidine pathway of Lactococcus lactis, two different pyrD genes encoding dihydroorotate dehydrogenase were isolated [4].

High impact information on URA1

• The heterologous expression of the Sch. pombe enzyme in S. cerevisiae allowed us to demonstrate that the Sch. pombe DHOdehase activity requires the integrity of the mitochondrial electron transport chain [5].
• By contrast, in vitro studies have revealed that the DHOdehase of S. cerevisiae uses fumarate as terminal electron acceptor [5].
• The DHOdehase from Sch. pombe was localized in the mitochondria whereas its homolog from S. cerevisiae was found to be cytosolic [5].
• Indeed, the presence of a mutation inactivating cytochrome b abolished the complementation of a S. cerevisiae ura1 mutant by the corresponding Sch. pombe gene [5].
• The promoters of the unlinked but coordinately regulated URA1 and URA4 genes contain highly conserved copies of the UASURA sequence, which prompted us to investigate the effects of many point mutations within this UASURA sequence on PPR1-dependent binding [6].

Biological context of URA1

• Nucleotide sequence of the URA1 gene of Saccharomyces cerevisiae [1].
• These deletion mutants display the wild-type basal level of URA1 and URA3 expression and show a semi-dominant phenotype in heteroallelic ppr1+/ppr1-delta diploids [7].
• There is an extensive alternating Pu:Py region including the T-A-T-A box of both promoters and an eight base-pair exact homology; further downstream, there is another 11 base-pair highly conserved sequence which either overlaps or lies in close proximity to the unregulated start sites of URA1 in S. pombe and of URA3 in S. cerevisiae [8].
• The library will thus be useful for the selection of cosmid clones which carry CDC genes from yeast by complementing first, with the vectorial yeast gene URA1, the pyrimidine auxotrophy of most cdc-strains and then, with the respective CDC wild-type genes, of the temperature-sensitive mutant alleles [9].
• Cosmids generated with arms from the most advanced vector, pMT6, carry the origin of replication (ori) and the ApR gene from pBR322 and the TRP1/ARS1 and URA1 genes from Saccharomyces cerevisiae [9].

Anatomical context of URA1

• Enzymatic activities of Ura2 and Ura1 proteins (aspartate carbamoyltransferase and dihydro-orotate dehydrogenase) are present in both isolated membranes and cytoplasm of Saccharomyces cerevisiae [10].
• Ultracytochemical localization of dihydroorotate dehydrogenase in mitochondria and vacuoles of Saccharomyces cerevisiae [11].

Associations of URA1 with chemical compounds

• The complete nucleotide sequence of the URA1 gene encoding dihydroorotic acid dehydrogenase (DHOdehase) is presented [1].
• Sequence analysis of the URA1 gene encoding orotidine-5'-monophosphate decarboxylase of Schizophyllum commune [3].
• The complete sequencing of a 24.6 kb segment of yeast chromosome XI identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open reading frames including homologues to the threonine dehydratases, membrane transporters, hydantoinases and the phospholipase A2-activating protein [12].
• It was also shown that the bacterially derived horizontally transferred DHOD is required for anaerobic synthesis of uracil in S. cerevisiae [13].

Other interactions of URA1

• Its organization and regulation indicate that the S. pombe URA1 gene product appears very similar to the S. cerevisiae URA2 gene product [14].
• No evidence of intracistronic complementation was found, and enzymatic analysis of leaky mutants did not reveal any mutations dissociating regulation of URA1 from that of URA3 [7].
• The APN1 locus is located approximately 235 kb from the left telomere of chromosome XI, and shows weak (approximately 53 cM) genetic linkage to ura1 [15].
• Identification of the known loci URA1, TRP3 and SAC1 revealed a translocation compared to the genetic map [12].

Analytical, diagnostic and therapeutic context of URA1

• Sequence analysis revealed that the coding region of the URA1 gene encompasses a polypeptide of 279 amino acids (aa) interrupted by two small introns [3].

References