New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism.
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.
Kurtz
J E
JE
Laboratoire de Génétique, UPR 9003 CNRS, Institut de Recherche contre les Cancers de l'Appareil Digestif, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, F-67091 Strasbourg Cedex, France.
Exinger
F
F
Erbs
P
P
Jund
R
R
D000595:Amino Acid Sequence; D002845:Chromatography; D003562:Cytidine / Q000031:analogs & derivatives / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000378:metabolism; D004351:Drug Resistance; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D010766:Phosphorylation; D017354:Point Mutation; D011743:Pyrimidines / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity; D014529:Uridine / Q000378:metabolism; D014541:Uridine Kinase / Q000378:metabolism
D011743:Pyrimidines; D003841:Deoxycytidine; D003562:Cytidine; D014541:Uridine Kinase; D003564:Cytidine Deaminase; C007745:5-fluorocytidine; D014529:Uridine