Although CRISPR/Cas9 system is a significant breakthrough and the most applied technique in gene editing, it can make unintended cuts in DNA. The Uri Ben-David team of the Broad Institute published a paper in Nature Genetics, shows that introduction of Cas9 can activate the p53 pathway in various cell lines and boost growth of cells with p53-inactivating mutations.
p53 gene is crucial for preventing cancer formation and therefore functions as a tumor suppressor in vertebrates. It is the guardian of genes and the shield protecting genes from mutation.
Additionally, the study found that the activity of Cas9 in normal p53 cell lines is much lower than that of p53 mutant cell lines, and the p53 pathway activation induced by Cas9 affects the sensitivity of cells to genetic and chemical screening, which in turn affects the screening results.
Reference:
Enache O M, Rendo V, Abdusamad M, et al. Cas9 activates the p53 pathway and selects for p53-inactivating mutations[J]. Nature Genetics, 2020: 1-7.
