Combinatorial CRISPR screen identifies fitness effects of gene paralogues.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33637726.
- Also identified by DOI 10.1038/s41467-021-21478-9 and PMC identifier 7910459.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CRISPR-Cas Systems
- Clustered Regularly Interspaced Short Palindromic Repeats
- Genome
- Proteins