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

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CONTENT BEING VIEWED BY OTHERS THE APPLICATION AND PROGRESSION OF CRISPR/CAS9 TECHNOLOGY IN OPHTHALMOLOGICAL DISEASES Article 01 August 2022 RESTORATION OF RPGR EXPRESSION IN VIVO USING

CRISPR/CAS9 GENE EDITING Article Open access 14 July 2021 COMPARISON OF CRISPR-CAS13B RNA BASE EDITING APPROACHES FOR USH2A-ASSOCIATED INHERITED RETINAL DEGENERATION Article Open access 08

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this work was carried out at the High Throughput Genome Engineering Facility and the Swedish National Genomics Infrastructure funded by Science for Life Laboratory (Scilifelab). The Knut and

Alice Wallenberg Foundation, Cancerfonden, Barncancerfonden and the Academy of Finland supported this work. We thank H. Han and Y. Bryceson for providing equipment, the Protein Science

Facility at Karolinska Institutet, as well as I. Sur and T. Kivioja for their comments on the manuscript. AUTHOR INFORMATION Author notes * These authors contributed equally: Emma

Haapaniemi, Sandeep Botla. * These authors jointly supervised this work: Bernhard Schmierer, Jussi Taipale. AUTHORS AND AFFILIATIONS * Department of Medical Biochemistry and Biophysics,

Karolinska Institute, Stockholm, Sweden Emma Haapaniemi, Sandeep Botla, Jenna Persson, Bernhard Schmierer & Jussi Taipale * Genome-Scale Biology Program, University of Helsinki,

Helsinki, Finland Emma Haapaniemi & Jussi Taipale * Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom Jussi Taipale Authors * Emma Haapaniemi View author

publications You can also search for this author inPubMed Google Scholar * Sandeep Botla View author publications You can also search for this author inPubMed Google Scholar * Jenna Persson

View author publications You can also search for this author inPubMed Google Scholar * Bernhard Schmierer View author publications You can also search for this author inPubMed Google Scholar

* Jussi Taipale View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS E.H., B.S. and J.T. wrote the manuscript. S.B., B.S. and J.P. conducted

the genome-wide knockout screens. E.H., B.S. and S.B. prepared the cell lines and performed the flow cytometry experiments. J.T. and B.S. supervised the study. All authors read and approved

the final manuscript. CORRESPONDING AUTHORS Correspondence to Bernhard Schmierer or Jussi Taipale. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests.

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Haapaniemi, E., Botla, S., Persson, J. _et al._ CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. _Nat Med_ 24, 927–930 (2018). https://doi.org/10.1038/s41591-018-0049-z

Download citation * Received: 11 September 2017 * Accepted: 23 April 2018 * Published: 11 June 2018 * Issue Date: July 2018 * DOI: https://doi.org/10.1038/s41591-018-0049-z SHARE THIS

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