Identification of Aneuploidy-Tolerating Mutations
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2013
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| Online Access: | http://hdl.handle.net/1721.1/82940 https://orcid.org/0000-0001-9837-0314 |
| _version_ | 1826189901902643200 |
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| author | Torres, Eduardo Martin Dephoure, Noah Panneerselvam, Amudha Tucker, Cheryl M. Whittaker, Charles A. Gygi, Steven P. Dunham, Maitreya J. Amon, Angelika B |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Torres, Eduardo Martin Dephoure, Noah Panneerselvam, Amudha Tucker, Cheryl M. Whittaker, Charles A. Gygi, Steven P. Dunham, Maitreya J. Amon, Angelika B |
| author_sort | Torres, Eduardo Martin |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:28:37Z |
| format | Article |
| id | mit-1721.1/82940 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:28:37Z |
| publishDate | 2013 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/829402022-09-30T09:21:48Z Identification of Aneuploidy-Tolerating Mutations Torres, Eduardo Martin Dephoure, Noah Panneerselvam, Amudha Tucker, Cheryl M. Whittaker, Charles A. Gygi, Steven P. Dunham, Maitreya J. Amon, Angelika B Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Torres, Eduardo Martin Panneerselvam, Amudha Whittaker, Charles A. Amon, Angelika B. 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. National Institutes of Health (U.S.) (grant P50 GM071508) Charles A. King Trust (Postdoctoral Research Fellowship Program) National Institutes of Health (U.S.) (grant GM56800) 2013-12-19T16:12:34Z 2013-12-19T16:12:34Z 2010-10 2010-06 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/82940 Torres, Eduardo M., Noah Dephoure, Amudha Panneerselvam, Cheryl M. Tucker, Charles A. Whittaker, Steven P. Gygi, Maitreya J. Dunham, and Angelika Amon. “Identification of Aneuploidy-Tolerating Mutations.” Cell 143, no. 1 (October 2010): 71-83. © 2010 Elsevier Inc. https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1016/j.cell.2010.08.038 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier B.V. Elsevier Open Archive |
| spellingShingle | Torres, Eduardo Martin Dephoure, Noah Panneerselvam, Amudha Tucker, Cheryl M. Whittaker, Charles A. Gygi, Steven P. Dunham, Maitreya J. Amon, Angelika B Identification of Aneuploidy-Tolerating Mutations |
| title | Identification of Aneuploidy-Tolerating Mutations |
| title_full | Identification of Aneuploidy-Tolerating Mutations |
| title_fullStr | Identification of Aneuploidy-Tolerating Mutations |
| title_full_unstemmed | Identification of Aneuploidy-Tolerating Mutations |
| title_short | Identification of Aneuploidy-Tolerating Mutations |
| title_sort | identification of aneuploidy tolerating mutations |
| url | http://hdl.handle.net/1721.1/82940 https://orcid.org/0000-0001-9837-0314 |
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