Title

Identification of aneuploidy-tolerating mutations

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

10-1-2010

Document Type

Article

Medical Subject Headings

*Aneuploidy; Cell Proliferation; Chromosome Aberrations; Endopeptidases; Gene Deletion; Humans; Neoplasms; Proteasome Endopeptidase Complex; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Ubiquitin

Disciplines

Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics | Molecular Biology | Molecular Genetics

Abstract

Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer. The mechanisms that allow cancer cells to tolerate the adverse effects of aneuploidy are not known. To probe this question, we identified aneuploid yeast strains with improved proliferative abilities. Their molecular characterization revealed strain-specific genetic alterations as well as mutations shared between different aneuploid strains. Among the latter, a loss-of-function mutation in the gene encoding the deubiquitinating enzyme Ubp6 improves growth rates in four different aneuploid yeast strains by attenuating the changes in intracellular protein composition caused by aneuploidy. Our results demonstrate the existence of aneuploidy-tolerating mutations that improve the fitness of multiple different aneuploidies and highlight the importance of ubiquitin-proteasomal degradation in suppressing the adverse effects of aneuploidy.

Rights and Permissions

Citation: Cell. 2010 Oct 1;143(1):71-83. doi: 10.1016/j.cell.2010.08.038. Epub 2010 Sep 16. Link to article on publisher's site

Comments

At the time of publication, Eduardo Torres was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

20850176