Aneuploidy Drives Genomic Instability in Yeast

David H. Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute (HHMI), Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (Impact Factor: 33.61). 08/2011; 333(6045):1026-30. DOI: 10.1126/science.1206412
Source: PubMed


Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer.

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Article: Aneuploidy Drives Genomic Instability in Yeast

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    • "While we were unable to classify these two groups based on gene expression differences, we did identify a list of 98 genes from across the genome all down-regulated in the chromosome 1q samples versus wild type. Aneuploidy work in yeast has shown that copy number alterations of chromosome arms can effect gene expression globally and is not limited to genes on the effected chromosome [31,32]. Our preliminary results here also indicate that the gain of chromosome 1q may have global effects on gene expression, and given its prevalence in early neoplasias associated with cancer, it may be important for the earliest stages of cancer development. "
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    • "DNA repair is significantly downregulated, which might lead to increased accumulation of DNA damage. The abundance changes in the DNA replication and repair factors might explain how aneuploidy increases genome instability, as has been observed in yeast [4] as well as in human aneuploids (S.S., V.P., Z.S., unpublished results). Further research should elucidate what are the causes of the consistent downregulation of DNA metabolism pathways and what consequences it brings upon aneuploid cells. "
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