Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting.

ABSTRACT:

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The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genom

SUBMITTER: Aguirre AJ 

PROVIDER: S-EPMC4972686 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature