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

被引:43
作者
Kurtz, JE [1 ]
Exinger, F [1 ]
Erbs, P [1 ]
Jund, R [1 ]
机构
[1] Hop Univ Strasbourg, Inst Rech Contre Canc Appareil Digest, UPR 9003 CNRS, Genet Lab, F-67091 Strasbourg, France
关键词
pyrimidine salvage pathway; cytidine deaminase; cytidine metabolism; CDD1; uridine/cytidine kinase;
D O I
10.1007/s002940050482
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:130 / 136
页数:7
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