Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance
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1752-0509-5-157.pdf
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Author(s)
Svensson, J. Peter
Quiros Pesudo, Laia
Fry, Rebecca C.
Adeleye, Yeyejide A.
Carmichael, Paul
Samson, Leona D
Date Issued
October 2011
Journal
BMC Systems Biology
Publisher
BioMed Central Ltd.
Citation
Svensson et al. "Genomic phenotyping of the essential and nonessential yeast genome detects novel pathways for alkylation resistance." BMC Systems Biology. 2011 Oct 06;5(1):157.
Version
Final published version
Abstract
Background: A myriad of new chemicals has been introduced into our environment and exposure to these agents can damage cells and induce cytotoxicity through different mechanisms, including damaging DNA directly. Analysis of global transcriptional and phenotypic responses in the yeast S. cerevisiae provides means to identify pathways of damage recovery upon toxic exposure. Results: Here we present a phenotypic screen of S. cerevisiae in liquid culture in a microtiter format. Detailed growth measurements were analyzed to reveal effects on ~5,500 different haploid strains that have either non-essential genes deleted or essential genes modified to generate unstable transcripts. The pattern of yeast mutants that are growth-inhibited (compared to WT cells) reveals the mechanisms ordinarily used to recover after damage. In addition to identifying previously-described DNA repair and cell cycle checkpoint deficient strains, we also identified new functional groups that profoundly affect MMS sensitivity, including RNA processing and telomere maintenance. Conclusions: We present here a data-driven method to reveal modes of toxicity of different agents that impair cellular growth. The results from this study complement previous genomic phenotyping studies as we have expanded the data to include essential genes and to provide detailed mutant growth analysis for each individual strain. This eukaryotic testing system could potentially be used to screen compounds for toxicity, to identify mechanisms of toxicity, and to reduce the need for animal testing.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1186/1752-0509-5-157
