1. Chromosomes and Gene Expression
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The genetic basis of aneuploidy tolerance in wild yeast

Research Article
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Cite this article as: eLife 2020;9:e52063 doi: 10.7554/eLife.52063

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 ssd1D 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.

Data availability

Sequencing data for genetic mapping are available in the Short Read Archive (SRA) under access number PRJNA548343, and MULTIPOOL output files are available in Dataset 1. RNA and RNA Immunoprecipitation (RIP) sequencing data are available from the GEO database under accession number GSE132425, and processed data are also available in Dataset 2. Raw proteomic data are available in the PRIDE database (Project accession # PXD013847); processed data are available in Dataset 2, and normalized protein abundance data are available in Dataset 3.

The following data sets were generated

Article and author information

Author details

  1. James Hose

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Leah E Escalante

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katie J Clowers

    Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. H Auguste Dutcher

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. DeElegant Robinson

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Venera Bouriakov

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Joshua J Coon

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Evgenia Shishkova

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Audrey P Gasch

    Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, United States
    For correspondence
    agasch@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8182-257X

Funding

National Cancer Institute ((R01CA229532)

  • Audrey P Gasch

Department of Energy (DE-SC0018409)

  • Joshua J Coon
  • Audrey P Gasch

National Institutes of Health (P41 GM108538)

  • Joshua J Coon

National Institutes of Health (T32 GM007133)

  • H Auguste Dutcher

National Institutes of Health (T32 HG002760)

  • DeElegant Robinson

National Science Foundation (GRFP)

  • Leah E Escalante

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hannah Klein, New York University School of Medicine, United States

Publication history

  1. Received: September 20, 2019
  2. Accepted: January 7, 2020
  3. Accepted Manuscript published: January 7, 2020 (version 1)
  4. Version of Record published: January 20, 2020 (version 2)

Copyright

© 2020, Hose et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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