Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance
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...
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| Format: | Article |
| Language: | en_US |
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Springer (Biomed Central Ltd.)
2012
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| Online Access: | http://hdl.handle.net/1721.1/69542 https://orcid.org/0000-0002-7112-1454 |
| _version_ | 1826217112206573568 |
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| author | Svensson, J. Peter Quiros Pesudo, Laia Fry, Rebecca C. Adeleye, Yeyejide A. Carmichael, Paul Samson, Leona D |
| author2 | Massachusetts Institute of Technology. Center for Environmental Health Sciences |
| author_facet | Massachusetts Institute of Technology. Center for Environmental Health Sciences Svensson, J. Peter Quiros Pesudo, Laia Fry, Rebecca C. Adeleye, Yeyejide A. Carmichael, Paul Samson, Leona D |
| author_sort | Svensson, J. Peter |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:58:13Z |
| format | Article |
| id | mit-1721.1/69542 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:58:13Z |
| publishDate | 2012 |
| publisher | Springer (Biomed Central Ltd.) |
| record_format | dspace |
| spelling | mit-1721.1/695422022-10-03T09:30:38Z Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance Svensson, J. Peter Quiros Pesudo, Laia Fry, Rebecca C. Adeleye, Yeyejide A. Carmichael, Paul Samson, Leona D 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 Samson, Leona D. Svensson, J. Peter Quiros Pesudo, Laia Samson, Leona D. Fry, Rebecca C. Adeleye, Yeyejide A. Carmichael, Paul 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. Unilever (Firm) National Institutes of Health (U.S.) (grant CA055042) National Institutes of Health (U.S.) (grant ES002109) Swedish Research Council Spanish Ministry of Science and Innovation 2012-03-01T17:43:19Z 2012-03-01T17:43:19Z 2011-10 2011-06 Article http://purl.org/eprint/type/JournalArticle 1752-0509 http://hdl.handle.net/1721.1/69542 Svensson, J Peter et al. “Genomic Phenotyping of the Essential and Non-essential Yeast Genome Detects Novel Pathways for Alkylation Resistance.” BMC Systems Biology 5.1 (2011): 157. Web. 1 Mar. 2012. https://orcid.org/0000-0002-7112-1454 en_US http://dx.doi.org/10.1186/1752-0509-5-157 BMC Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 application/pdf Springer (Biomed Central Ltd.) |
| spellingShingle | Svensson, J. Peter Quiros Pesudo, Laia Fry, Rebecca C. Adeleye, Yeyejide A. Carmichael, Paul Samson, Leona D Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title | Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title_full | Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title_fullStr | Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title_full_unstemmed | Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title_short | Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance |
| title_sort | genomic phenotyping of the essential and non essential yeast genome detects novel pathways for alkylation resistance |
| url | http://hdl.handle.net/1721.1/69542 https://orcid.org/0000-0002-7112-1454 |
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