Homologous recombination

Gene

Cell cycle checkpoint

Cas9

DNA repair

Function (biology)

Genome

DNA damage

Genome editing

Cell

Cell cycle

Mutation

Genetics

Computational biology

Biology

Cell biology

CRISPR

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 genome editing induces a p53-mediated DNA damage response