Use of synthetic lethal mutants to clone and characterize a novel CTP synthetase gene in Saccharomyces cerevisiae

Odile Ozier-Kalogeropoulos, Marie Thérèse Adeline, Weng Lang Yang, George M. Carman, François Lacroute

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

In the pyrimidine biosynthetic pathway, CTP synthetase catalyses the conversion of uridine 5′-triphosphate (UTP) to cytidine 5′-triphosphate (CTP). In the yeast Saccharomyces cerevisiae, the URA7 gene encoding this enzyme was previously shown to be nonessential for cell viability. The present paper describes the selection of synthetic lethal mutants in the CTP biosynthetic pathway that led us to clone a second gene, named URA8, which also encodes a CTP synthetase. Comparison of the predicted amino acid sequences of the products of URA7 and URA8 shows 78% identity. Deletion of the URA8 gene is viable in a haploid strain but simultaneous presence of null alleles both URA7 and URA8 is lethal. Based on the codon bias values for the two genes and the intracellular concentrations of CTP in strains deleted for one of the two genes, relative to the wild-type level, URA7 appears to be the major gene for CTP biosynthesis. Nevertheless, URA8 alone also allows yeast growth, at least under standard laboratory conditions.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalMGG Molecular & General Genetics
Volume242
Issue number4
DOIs
StatePublished - Feb 1994

Keywords

  • CTP synthetase
  • Duplicate genes
  • Pyrimidine biosynthetic pathway
  • Saccharomyces cerevisiae
  • Synthetic lethal mutants

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Use of synthetic lethal mutants to clone and characterize a novel CTP synthetase gene in Saccharomyces cerevisiae'. Together they form a unique fingerprint.

Cite this