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Title: The genetic basis of aneuploidy tolerance in wild yeast

Abstract

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.

Authors:
 [1];  [2];  [3];  [2];  [1];  [4];  [5];  [6]; ORCiD logo [7]
  1. Center for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States
  2. Center for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States, Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
  3. Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
  4. Center for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States, Great Lakes Bioenergy Research Center, Madison, United States
  5. Center 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 States
  6. Center for Genomic Science Innovation, University of Wisconsin–Madison, Madison, United States, Morgridge Institute for Research, Madison, United States
  7. Center 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 States
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1581463
Alternate Identifier(s):
OSTI ID: 1581464
Grant/Contract Number:  
SC0018409
Resource Type:
Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Name: eLife Journal Volume: 9; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English

Citation Formats

Hose, James, Escalante, Leah E., Clowers, Katie J., Dutcher, H. Auguste, Robinson, DeElegant, Bouriakov, Venera, Coon, Joshua J., Shishkova, Evgenia, and Gasch, Audrey P. The genetic basis of aneuploidy tolerance in wild yeast. United States: N. p., 2020. Web. doi:10.7554/eLife.52063.
Hose, James, Escalante, Leah E., Clowers, Katie J., Dutcher, H. Auguste, Robinson, DeElegant, Bouriakov, Venera, Coon, Joshua J., Shishkova, Evgenia, & Gasch, Audrey P. The genetic basis of aneuploidy tolerance in wild yeast. United States. doi:10.7554/eLife.52063.
Hose, James, Escalante, Leah E., Clowers, Katie J., Dutcher, H. Auguste, Robinson, DeElegant, Bouriakov, Venera, Coon, Joshua J., Shishkova, Evgenia, and Gasch, Audrey P. Tue . "The genetic basis of aneuploidy tolerance in wild yeast". United States. doi:10.7554/eLife.52063.
@article{osti_1581463,
title = {The genetic basis of aneuploidy tolerance in wild yeast},
author = {Hose, James and Escalante, Leah E. and Clowers, Katie J. and Dutcher, H. Auguste and Robinson, DeElegant and Bouriakov, Venera and Coon, Joshua J. and Shishkova, Evgenia and Gasch, Audrey P.},
abstractNote = {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.},
doi = {10.7554/eLife.52063},
journal = {eLife},
number = ,
volume = 9,
place = {United States},
year = {2020},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.7554/eLife.52063

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