Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.pdf (4.12 MB)
Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness
journal contribution
posted on 2023-06-10, 04:23 authored by Federica Schiavoni, Pedro Zuazua-Villar, Theodoros I Roumeliotis, Graeme Benstead-Hume, Mercedes Pardo, Frances PearlFrances Pearl, Jyoti S Choudhary, Jessica A DownsAneuploidy 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.
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature ResearchExternal DOI
Volume
13Page range
1-15Event location
EnglandDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-08-03First Open Access (FOA) Date
2022-08-03First Compliant Deposit (FCD) Date
2022-08-02Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC