Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast

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Abstract

Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms.

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Noah Dephoure

Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Sunyoung Hwang

University of Massachusetts Medical School, Worcester, United States

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The authors declare that no competing interests exist.
Ciara O'Sullivan

University of Massachusetts Medical School, Worcester, United States

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The authors declare that no competing interests exist.
Stacie E Dodgson

Massachusetts Institute of Technology, Cambridge, United States

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The authors declare that no competing interests exist.
Steve P Gygi

Harvard Medical School, Boston, United States

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The authors declare that no competing interests exist.
Angelika Amon

Massachusetts Institute of Technology, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Eduardo M Torres

University of Massachusetts Medical School, Worcester, United States

For correspondence
eduardo.torres@umassmed.edu

Competing interests
The authors declare that no competing interests exist.

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