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

2018; Nature Portfolio; Volume: 24; Issue: 7 Linguagem: Inglês

10.1038/s41591-018-0049-z

1546-170X

Emma Haapaniemi, Sandeep K. Botla, Jenna Persson, Bernhard Schmierer, Jussi Taipale,

Cytomegalovirus and herpesvirus research

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.