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    Combinatorial CRISPR screen identifies fitness effects of gene paralogues

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    Authors
    Thompson, N. A.
    Ranzani, M.
    van der Weyden, L.
    Iyer, V.
    Offord, V.
    Droop, A.
    Behan, F.
    Gonçalves, E.
    Speak, A.
    Iorio, F.
    Hewinson, J.
    Harle, V.
    Robertson, H.
    Anderson, E.
    Fu, B.
    Yang, F.
    Zagnoli-Vieira, G.
    Chapman, Phil
    Del Castillo Velasco-Herrera, M.
    Garnett, M. J.
    Jackson, S. P.
    Adams, D. J.
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    Affiliation
    Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge
    Issue Date
    2021
    
    Metadata
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    Abstract
    Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells.
    Citation
    Thompson NA, Ranzani M, van der Weyden L, Iyer V, Offord V, Droop A, et al. Combinatorial CRISPR screen identifies fitness effects of gene paralogues. Nat Commun. 2021;12(1):1302.
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/623850
    DOI
    10.1038/s41467-021-21478-9
    PubMed ID
    33637726
    Additional Links
    https://dx.doi.org/10.1038/s41467-021-21478-9
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-021-21478-9
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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