| Literature DB >> 33637726 |
Marco Ranzani1, Louise van der Weyden1, Nicola A Thompson1, Vivek Iyer1, Victoria Offord1, Alastair Droop1, Fiona Behan1, Emanuel Gonçalves1, Anneliese Speak1, Francesco Iorio1,2, James Hewinson1, Victoria Harle1, Holly Robertson1, Elizabeth Anderson1, Beiyuan Fu1, Fengtang Yang1, Guido Zagnoli-Vieira3, Phil Chapman4, Martin Del Castillo Velasco-Herrera1, Mathew J Garnett1, Stephen P Jackson3, David J Adams5.
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.Entities:
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Year: 2021 PMID： 33637726 PMCID： PMC7910459 DOI： 10.1038/s41467-021-21478-9
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919