Department of Molecular, Cell and Cancer Biology
Cell and Developmental Biology | Cellular and Molecular Physiology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Molecular Biology | Nervous System Diseases
An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases.
Down syndrome, Edwards, Patau, aneuploidy, long-chain base, nuclear envelope, nuclear morphology, sphingolipid, sphingosine, trisomy 21
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Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2019 Nov 19;29(8):2473-2488.e5. doi: 10.1016/j.celrep.2019.10.059. Link to article on publisher's site
Hwang S, Williams JF, Kneissig M, Lioudyno M, Rivera I, Helguera P, Busciglio J, Storchova Z, King MC, Torres EM. (2019). Suppressing Aneuploidy-Associated Phenotypes Improves the Fitness of Trisomy 21 Cells. Open Access Articles. https://doi.org/10.1016/j.celrep.2019.10.059. Retrieved from https://escholarship.umassmed.edu/oapubs/4045
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Cell and Developmental Biology Commons, Cellular and Molecular Physiology Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Molecular Biology Commons, Nervous System Diseases Commons