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Open Access Research article

Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast

Elena I Stepchenkova1, Stanislav G Kozmin12, Vladimir V Alenin1 and Youri I Pavlov13*

Author Affiliations

1 Department of Genetics, Sankt-Petersburg State University, Sankt-Petersburg, 199034, Russia

2 Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, RTP, NC 27709, USA

3 Eppley Institute for Research in Cancer and Allied Diseases, the Department of Biochemistry and Molecular Biology, and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA

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BMC Genetics 2005, 6:31  doi:10.1186/1471-2156-6-31

Published: 2 June 2005

Abstract

Background

N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA), are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast.

Results

We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism.

Conclusion

We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA.