CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. (July 2018)

• Record Type: Journal Article
• Authors: Haapaniemi, Emma; Botla, Sandeep; Persson, Jenna; Schmierer, Bernhard; Taipale, Jussi
• Is Part Of: Nature medicine. Volume 24:Number 7(2018)
• Page Start: 927
• Page End: 930
• Publication Date: 2018-07
• Subjects: Pathology, Molecular -- Periodicals; Molecular biology -- Periodicals; 610.724
• DOI: 10.1038/s41591-018-0049-z
• Languages: English
• ISSNs: 1078-8956

Abstract

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. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in immortalized human retinal pigment epithelial cells.