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dc.contributor.authorSchiavoni, F
dc.contributor.authorZuazua-Villar, P
dc.contributor.authorRoumeliotis, TI
dc.contributor.authorBenstead-Hume, G
dc.contributor.authorPardo, M
dc.contributor.authorPearl, FMG
dc.contributor.authorChoudhary, JS
dc.contributor.authorDowns, JA
dc.coverage.spatialEngland
dc.date.accessioned2022-06-17T12:36:07Z
dc.date.available2022-06-17T12:36:07Z
dc.date.issued2022-04-01
dc.identifierARTN 1731
dc.identifier10.1038/s41467-022-29420-3
dc.identifier.citationNature Communications, 2022, 13 (1), pp. 1731 -en_US
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5183
dc.identifier.eissn2041-1723
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-022-29420-3
dc.identifier.doi10.1038/s41467-022-29420-3
dc.description.abstractAneuploidy 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.
dc.formatElectronic
dc.format.extent1731 -
dc.languageeng
dc.language.isoengen_US
dc.publisherNATURE PORTFOLIOen_US
dc.relation.ispartofNature Communications
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAneuploidy
dc.subjectCell Line
dc.subjectChromatin Assembly and Disassembly
dc.subjectChromosome Aberrations
dc.subjectChromosomes
dc.subjectDNA Helicases
dc.subjectHumans
dc.subjectNuclear Proteins
dc.subjectTranscription Factors
dc.titleAneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-03-16
dc.date.updated2022-06-17T12:35:22Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1038/s41467-022-29420-3en_US
rioxxterms.licenseref.startdate2022-04-01
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35365638
pubs.issue1
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Epigenetics and Genome Stability
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group
pubs.organisational-group/ICR/ImmNet
pubs.publication-statusPublished online
pubs.volume13
icr.researchteamFunctional Proteomicsen_US
icr.researchteamProte & Metabolomics Facen_US
icr.researchteamGenome Stabilityen_US
dc.contributor.icrauthorPardo Calvo, Maria Mercedes
dc.contributor.icrauthorChoudhary, Jyoti
dc.contributor.icrauthorDowns, Jessica


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