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

Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J

Nat Med - (-) - [2018-06-11; online 2018-06-11]

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.

High-throughput Genome Engineering (HTGE) [Collaborative]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

Protein Science Facility (PSF) [Service]

PubMed 29892067

DOI 10.1038/s41591-018-0049-z

Crossref 10.1038/s41591-018-0049-z