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Nat Med. 2018 Jul;24(7):927-930. doi: 10.1038/s41591-018-0049-z. Epub 2018 Jun 11.

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

Author information

1
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
2
Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland.
3
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. bernhard.schmierer@ki.se.
4
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. ajt208@cam.ac.uk.
5
Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland. ajt208@cam.ac.uk.
6
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom. ajt208@cam.ac.uk.

Abstract

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.

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PMID:
29892067
DOI:
10.1038/s41591-018-0049-z
[Indexed for MEDLINE]

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