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• W2908955301 abstract "ABSTRACT Rapid mutation fuels the evolution of many cancers and pathogens. Much of the ensuing genetic variation is detrimental, but cells can survive by limiting the cost of accumulating mutation burden. We investigated this behavior by propagating hypermutating yeast lineages to create independent populations harboring thousands of distinct genetic variants. Mutation rate and spectrum remained unchanged throughout the experiment, yet lesions that arose early were more deleterious than those that arose later. Although the lineages shared no mutations in common, each mounted a similar transcriptional response to mutation burden. The proteins involved in this response formed a highly connected network that has not previously been identified. Inhibiting this response increased the cost of accumulated mutations, selectively killing highly mutated cells. A similar gene expression program exists in hypermutating human cancers and is linked to survival. Our data thus define a conserved stress response that buffers the cost of accumulating genetic lesions and further suggest that this network could be targeted therapeutically." @default.
• W2908955301 created "2019-01-25" @default.
• W2908955301 creator A5025891289 @default.
• W2908955301 creator A5026586527 @default.
• W2908955301 creator A5066860900 @default.
• W2908955301 creator A5076881981 @default.
• W2908955301 creator A5088326542 @default.
• W2908955301 creator A5088766030 @default.
• W2908955301 date "2019-01-09" @default.
• W2908955301 modified "2023-09-24" @default.
• W2908955301 title "A stress response that allows highly mutated eukaryotic cells to survive and proliferate" @default.
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