Program in Gene Function and Expression
Cell Biology | Computational Biology | Genetics and Genomics
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.
aneuploidy, posttranscriptional mechanisms, posttranslational mechanisms, proteomics
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Copyright Dephoure et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, Torres EM. Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast. Elife. 2014 Jul 29;3:e03023. doi: 10.7554/eLife.03023. Link to article on publisher's site
Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E.; Gygi, Steven P.; Amon, Angelika; and Torres, Eduardo M., "Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast" (2014). Program in Gene Function and Expression Publications and Presentations. 252.