CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response
CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response
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DOI：
10.1038/s41591-018-0049-z
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发表时间：
2018-07-01
期刊：
影响因子：
82.9
通讯作者：
Taipale, Jussi
中科院分区：
文献类型：
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作者：
Haapaniemi, Emma;Botla, Sandeep;Taipale, Jussi
在这里，我们报道了CRISPR-Cas9的基因组编辑在永生化的人视网膜色素上皮细胞中诱导p53介导的DNA损伤反应和细胞周期阻滞，导致对具有功能p53通路的细胞的选择。抑制p53可防止损伤反应，并增加来自供体模板的同源重组率。这些结果表明，抑制p53可能会提高未转化细胞的基因组编辑效率，在利用CRISPR-Cas9开发基于细胞的疗法时，应该监测p53的功能。
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.