The genetic basis of aneuploidy tolerance in wild yeast
Aneuploidy is highly detrimental during development yet common in cancers and pathogenic fungi – what gives rise to differences in aneuploidy tolerance remains unclear. We previously showed that wild isolates of Saccharomyces cerevisiae tolerate chromosome amplification while laboratory strains used...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52063 |
| _version_ | 1811199586873638912 |
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| author | James Hose Leah E Escalante Katie J Clowers H Auguste Dutcher DeElegant Robinson Venera Bouriakov Joshua J Coon Evgenia Shishkova Audrey P Gasch |
| author_facet | James Hose Leah E Escalante Katie J Clowers H Auguste Dutcher DeElegant Robinson Venera Bouriakov Joshua J Coon Evgenia Shishkova Audrey P Gasch |
| author_sort | James Hose |
| collection | DOAJ |
| description | Aneuploidy is highly detrimental during development yet common in cancers and pathogenic fungi – what gives rise to differences in aneuploidy tolerance remains unclear. We previously showed that wild isolates of Saccharomyces cerevisiae tolerate chromosome amplification while laboratory strains used as a model for aneuploid syndromes do not. Here, we mapped the genetic basis to Ssd1, an RNA-binding translational regulator that is functional in wild aneuploids but defective in laboratory strain W303. Loss of SSD1 recapitulates myriad aneuploidy signatures previously taken as eukaryotic responses. We show that aneuploidy tolerance is enabled via a role for Ssd1 in mitochondrial physiology, including binding and regulating nuclear-encoded mitochondrial mRNAs, coupled with a role in mitigating proteostasis stress. Recapitulating ssd1Δ defects with combinatorial drug treatment selectively blocked proliferation of wild-type aneuploids compared to euploids. Our work adds to elegant studies in the sensitized laboratory strain to present a mechanistic understanding of eukaryotic aneuploidy tolerance. |
| first_indexed | 2024-04-12T01:50:02Z |
| format | Article |
| id | doaj.art-015b68d9383a453c8abee8df8945d841 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:50:02Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-015b68d9383a453c8abee8df8945d8412022-12-22T03:52:57ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.52063The genetic basis of aneuploidy tolerance in wild yeastJames Hose0Leah E Escalante1Katie J Clowers2H Auguste Dutcher3DeElegant Robinson4Venera Bouriakov5Joshua J Coon6Evgenia Shishkova7Audrey P Gasch8https://orcid.org/0000-0002-8182-257XCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Laboratory of Genetics, University of Wisconsin-Madison, Madison, United StatesLaboratory of Genetics, University of Wisconsin-Madison, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Laboratory of Genetics, University of Wisconsin-Madison, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Great Lakes Bioenergy Research Center, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Great Lakes Bioenergy Research Center, Madison, United States; Department of Biomolecular Chemistry, University of Wisconsin–Madison, Madison, United States; Department of Chemistry, University of Wisconsin–Madison, Madison, United States; Morgridge Institute for Research, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Morgridge Institute for Research, Madison, United StatesCenter for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States; Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States; Great Lakes Bioenergy Research Center, Madison, United StatesAneuploidy is highly detrimental during development yet common in cancers and pathogenic fungi – what gives rise to differences in aneuploidy tolerance remains unclear. We previously showed that wild isolates of Saccharomyces cerevisiae tolerate chromosome amplification while laboratory strains used as a model for aneuploid syndromes do not. Here, we mapped the genetic basis to Ssd1, an RNA-binding translational regulator that is functional in wild aneuploids but defective in laboratory strain W303. Loss of SSD1 recapitulates myriad aneuploidy signatures previously taken as eukaryotic responses. We show that aneuploidy tolerance is enabled via a role for Ssd1 in mitochondrial physiology, including binding and regulating nuclear-encoded mitochondrial mRNAs, coupled with a role in mitigating proteostasis stress. Recapitulating ssd1Δ defects with combinatorial drug treatment selectively blocked proliferation of wild-type aneuploids compared to euploids. Our work adds to elegant studies in the sensitized laboratory strain to present a mechanistic understanding of eukaryotic aneuploidy tolerance.https://elifesciences.org/articles/52063aneuploidynatural variationproteotoxicitywild strains |
| spellingShingle | James Hose Leah E Escalante Katie J Clowers H Auguste Dutcher DeElegant Robinson Venera Bouriakov Joshua J Coon Evgenia Shishkova Audrey P Gasch The genetic basis of aneuploidy tolerance in wild yeast eLife aneuploidy natural variation proteotoxicity wild strains |
| title | The genetic basis of aneuploidy tolerance in wild yeast |
| title_full | The genetic basis of aneuploidy tolerance in wild yeast |
| title_fullStr | The genetic basis of aneuploidy tolerance in wild yeast |
| title_full_unstemmed | The genetic basis of aneuploidy tolerance in wild yeast |
| title_short | The genetic basis of aneuploidy tolerance in wild yeast |
| title_sort | genetic basis of aneuploidy tolerance in wild yeast |
| topic | aneuploidy natural variation proteotoxicity wild strains |
| url | https://elifesciences.org/articles/52063 |
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