New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism.

Abstract

Cytidine metabolism in the yeast Saccharomyces cerevisiae was analyzed by genetic and biochemical approaches. Disruption of a unique ORF (Genbank accession No. U 20865) bearing homology with eucaryotic or bacterial cytidine deaminases abolished cytidine deaminase activity and resulted in 5-fluorocytidine resistance. The gene encoding cytidine deaminase will be referred to as CDD1 (Genbank accession number AF080089). The ability to isolate mutants resistant to 5-fluorocytidine which mapped to five other loci demonstrated the existence of a complex cytidine metabolic network. Deciphering this network revealed several original features:(1) cytidine entry is mediated by the purine-cytosine transporter (Fcy2p),(2) cytidine is cleaved into cytosine by the uridine nucleosidase (Urh1p),(3) cytidine is phosphorylated into CMP by the uridine kinase (Urk1p),(4) a block in cytosine deaminase (Fcy1p), but not in cytidine deaminase (Cdd1p), constitutes a limiting step in cytidine utilisation as a UMP precursor.

• Authors: J E Kurtz, F Exinger, P Erbs, R Jund
• Journal: Current genetics (Curr Genet) Vol. 36 Issue 3 Pg. 130-6 (Sep 1999) ISSN: 0172-8083 [Print] United States
• PMID: 10501935 (Publication Type: Journal Article)

Chemical References

• Pyrimidines
• Deoxycytidine
• Cytidine
• Uridine Kinase
• Cytidine Deaminase
• 5-fluorocytidine
• Uridine

Topics

• Amino Acid Sequence
• Chromatography
• Cytidine (analogs & derivatives, genetics, metabolism, pharmacology)
• Cytidine Deaminase (genetics, metabolism)
• Deoxycytidine (metabolism)
• Drug Resistance
• Models, Biological
• Molecular Sequence Data
• Phenotype
• Phosphorylation
• Point Mutation
• Pyrimidines (metabolism)
• Saccharomyces cerevisiae (drug effects, genetics)
• Sequence Analysis, DNA
• Substrate Specificity
• Uridine (metabolism)
• Uridine Kinase (metabolism)