Identification of Aneuploidy-Tolerating Mutations

被引：294

作者：

Torres, Eduardo M. ^{[1
,2
]}

Dephoure, Noah ^{[3
]}

Panneerselvam, Amudha ^{[1
]}

Tucker, Cheryl M. ^{[4
]}

Whittaker, Charles A. ^{[1
]}

Gygi, Steven P. ^{[3
]}

Dunham, Maitreya J. ^{[5
]}

Amon, Angelika ^{[1
,2
]}

机构：

[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[2] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[3] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[4] Princeton Univ, Lewis Sigler Inst, Princeton, NJ 08540 USA

[5] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

来源：

CELL | 2010年 / 143卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL INSTABILITY; YEAST; DEGRADATION; PROTEASOME; CELLS; DEUBIQUITINATION; DEPLETION; CODE;

D O I：

10.1016/j.cell.2010.08.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：71 / 83

页数：13

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