DNA repair

DNA damage

Cell

Biology

Homologous recombination

Gene

Cell cycle checkpoint

Genome editing

Cas9

Function (biology)

Genome

Cell cycle

Mutation

Computational biology

Cell biology

CRISPR

Genetics

Nature Medicine

Here, we report that genome editing by CRISPR–Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR–Cas9. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.

CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response