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Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, Torres EM - Elife (2014)

Bottom Line: Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

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Related in: MedlinePlus

Proliferation capabilities of aneuploid cells in the presence of 3% H2O2.(A) Proliferation capabilities of WT, disomes and cells harboring YACs on YEPD medium alone or in the presence of 3% H2O2. (B) FACS analysis of cells grown in YEPD medium stained CM-H2DCFDA.DOI:http://dx.doi.org/10.7554/eLife.03023.028
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fig6s4: Proliferation capabilities of aneuploid cells in the presence of 3% H2O2.(A) Proliferation capabilities of WT, disomes and cells harboring YACs on YEPD medium alone or in the presence of 3% H2O2. (B) FACS analysis of cells grown in YEPD medium stained CM-H2DCFDA.DOI:http://dx.doi.org/10.7554/eLife.03023.028

Mentions: Our proteome analysis revealed a response to oxidative stress in aneuploid yeast strains. To test whether this was due to defects in redox homeostasis, we compared the viability of wild-type cells and disomes in the presence of diamide or hydrogen peroxide (H2O2). We found that most disomes show hypersensitivity to the reactive oxygen species ROS-inducing agents diamide (1 mM) or H2O2 (3%) (Figure 6D, Figure 6—figure supplement 4A). To investigate whether the mere presence of chromosome-size amounts of DNA was responsible for hypersensitivity to diamide or H2O2, we tested the viability of strains harboring a yeast artificial chromosome (YAC) varying in size containing human or mouse DNA. Cells harboring such YACs did not exhibit hypersensitivity to the ROS inducing agents (Figure 6D, Figure 6—figure supplement 4A), indicating that the presence of the extra yeast genes and their products is responsible for the increased sensitivity to oxidative stress.


Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

Dephoure N, Hwang S, O'Sullivan C, Dodgson SE, Gygi SP, Amon A, Torres EM - Elife (2014)

Proliferation capabilities of aneuploid cells in the presence of 3% H2O2.(A) Proliferation capabilities of WT, disomes and cells harboring YACs on YEPD medium alone or in the presence of 3% H2O2. (B) FACS analysis of cells grown in YEPD medium stained CM-H2DCFDA.DOI:http://dx.doi.org/10.7554/eLife.03023.028
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129440&req=5

fig6s4: Proliferation capabilities of aneuploid cells in the presence of 3% H2O2.(A) Proliferation capabilities of WT, disomes and cells harboring YACs on YEPD medium alone or in the presence of 3% H2O2. (B) FACS analysis of cells grown in YEPD medium stained CM-H2DCFDA.DOI:http://dx.doi.org/10.7554/eLife.03023.028
Mentions: Our proteome analysis revealed a response to oxidative stress in aneuploid yeast strains. To test whether this was due to defects in redox homeostasis, we compared the viability of wild-type cells and disomes in the presence of diamide or hydrogen peroxide (H2O2). We found that most disomes show hypersensitivity to the reactive oxygen species ROS-inducing agents diamide (1 mM) or H2O2 (3%) (Figure 6D, Figure 6—figure supplement 4A). To investigate whether the mere presence of chromosome-size amounts of DNA was responsible for hypersensitivity to diamide or H2O2, we tested the viability of strains harboring a yeast artificial chromosome (YAC) varying in size containing human or mouse DNA. Cells harboring such YACs did not exhibit hypersensitivity to the ROS inducing agents (Figure 6D, Figure 6—figure supplement 4A), indicating that the presence of the extra yeast genes and their products is responsible for the increased sensitivity to oxidative stress.

Bottom Line: Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.

Show MeSH
Related in: MedlinePlus