title: The exceptionally high rate of spontaneous mutations in the polymerase delta proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine.
abstract: BACKGROUND
  Mutagenesis induced in the yeast Saccharomyces cerevisiae by starvation for nutrilites is a well-documented phenomenon of an unknown mechanism. We have previously shown that the polymerase delta proofreading activity controls spontaneous mutagenesis in cells starved for histidine. To obtain further information, we compared the effect of adenine starvation on mutagenesis in wild-type cells and, in cells lacking the proofreading activity of polymerase delta (phenotype Exo-, mutation pol3-01).
  
  
  RESULTS
  Ade+ revertants accumulated at a very high rate on adenine-free plates so that their frequency on day 16 after plating was 1.5 x 10(-4) for wild-type and 1.0 x 10(-2) for the Exo- strain. In the Exo- strain, all revertants arising under adenine starvation are suppressors of the original mutation, most possessed additional nutritional requirements, and 50% of them were temperature sensitive.
  
  
  CONCLUSIONS
  Adenine starvation is highly mutagenic in yeast. The deficiency in the polymerase delta proofreading activity in strains with the pol3-01 mutation leads to a further 66-fold increase of the rate of mutations. Our data suggest that adenine starvation induces genome-wide hyper-mutagenesis in the Exo- strain.
authors.affiliation: Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia, Italy. achilli@ipvgen.unipv.it <achilli@ipvgen.unipv.it>
authors.forename: Alessandro
authors.initials: A
authors.lastname: Achilli
authors.forename: Nabil
authors.initials: N
authors.lastname: Matmati
authors.forename: Enrico
authors.initials: E
authors.lastname: Casalone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Morpurgo
authors.forename: Angela
authors.initials: A
authors.lastname: Lucaccioni
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
authors.forename: Nora
authors.initials: N
authors.lastname: Babudri
mesh_terms: D000225:Adenine / Q000494:pharmacology*; D004258:DNA Polymerase III / Q000502:physiology*; D005092:Exonucleases / Q000172:deficiency*; D016681:Genome, Fungal / Q000235:genetics; D007700:Kinetics; D016296:Mutagenesis; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D004258:DNA Polymerase III; D005092:Exonucleases; D000225:Adenine