Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.
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Authors
Schiavoni, F
Zuazua-Villar, P
Roumeliotis, TI
Benstead-Hume, G
Pardo, M
Pearl, FMG
Choudhary, JS
Downs, JA
Zuazua-Villar, P
Roumeliotis, TI
Benstead-Hume, G
Pardo, M
Pearl, FMG
Choudhary, JS
Downs, JA
Document Type
Journal Article
Date
2022-04-01
Date Accepted
2022-03-16
Abstract
Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy on cellular fitness is context dependent. The BRG1 (SMARCA4) subunit of the SWI/SNF chromatin remodelling complex is frequently lost in cancer. Here, we use a chromosomally stable cell line to test the effect of BRG1 loss on the evolution of aneuploidy. BRG1 deletion leads to an initial loss of fitness in this cell line that improves over time. Notably, we find increased tolerance to aneuploidy immediately upon loss of BRG1, and the fitness recovery over time correlates with chromosome gain. These data show that BRG1 loss creates an environment where karyotype changes can be explored without a fitness penalty. At least in some genetic backgrounds, therefore, BRG1 loss can affect the progression of tumourigenesis through tolerance of aneuploidy.
Citation
Nature Communications, 2022, 13 (1), pp. 1731 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Functional Proteomics
Prote & Metabolomics Fac
Genome Stability
Prote & Metabolomics Fac
Genome Stability