Research article

The exceptionally high rate of spontaneous mutations in the polymerase delta proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine

Alessandro Achilli¹ , Nabil Matmati² , Enrico Casalone³ , Giorgio Morpurgo⁴ , Angela Lucaccioni⁴ , Youri I Pavlov⁵ and Nora Babudri⁴

¹Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia, Italy

²Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA

³Dipartimento di Biologia Animale e Genetica, Università di Firenze, Firenze, Italy

⁴Dipartimento di Biologia Cellulare e Molecolare, Università degli Studi di Perugia, Perugia, Italy

⁵Eppley Institute for Research in Cancer and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA

author email corresponding author email

BMC Genetics 2004, 5:34doi:10.1186/1471-2156-5-34

Published:	23 December 2004

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 × 10^-4 for wild-type and 1.0 × 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.