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Identification of aneuploidy-tolerating mutations.

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.

SUBMITTER: Torres EM

PROVIDER: S-EPMC2993244 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Identification of aneuploidy-tolerating mutations.

Torres Eduardo M EM Dephoure Noah N Panneerselvam Amudha A Tucker Cheryl M CM Whittaker Charles A CA Gygi Steven P SP Dunham Maitreya J MJ Amon Angelika A

Cell 20100916 1

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 b ...[more]

PMID: 20850176

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Project description:This study demonstrates the appearance of super intense and wide Mie bandgaps in metamaterials composed of tellurium, germanium, and silicon rods in air that tolerate some disordering of rod position and rod radius under transverse magnetic (TM) polarized light waves. Tellurium metamaterials reveal [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] Mie bandgap modes in which [Formula: see text], [Formula: see text], and [Formula: see text] tolerate high rod-position disordering of [Formula: see text] and rod-radius disordering of 34 and [Formula: see text], respectively. Results for germanium metamaterials show Mie bandgap modes [Formula: see text], [Formula: see text], and [Formula: see text], in which [Formula: see text] and [Formula: see text] tolerate rod-position disordering of [Formula: see text], and rod-radius disordering of 34 and [Formula: see text], respectively. Using these characteristics of [Formula: see text] in germanium metamaterials under position and radius disordering, ultra-narrow straight, L-shaped, and crossing waveguides that contain 14, four, and two rows of germanium rods in air are designed. Also, it is shown that [Formula: see text] Mie bandgap appears in metamaterials containing a high refractive index, and disappears in metamaterials with a lower refractive index such as silicon; in contrast, a new phenomenon of intense and broadband [Formula: see text], [Formula: see text], and [Formula: see text] in metamaterials with a lower refractive index such as silicon appear. In silicon-based metamaterials, [Formula: see text] tolerates high rod-position and rod-radius disordering of [Formula: see text] and [Formula: see text], respectively, and [Formula: see text] shows robustness to rod-position and rod-radius disordering of [Formula: see text]. This strong tolerance of disordering of TM modes in tellurium, germanium, and silicon metamaterials opens a new way to design small, high-efficient, and feasible fabrication optical devices for optical integrated circuits.

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Identification of aneuploidy-tolerating mutations.

Publications

Identification of aneuploidy-tolerating mutations.

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