Adding to the CASeload: unwarranted p53 signaling induced by Cas9

Veronica Rendo; Oana M Enache; Uri Ben-David

doi:10.1080/23723556.2020.1789419

Adding to the CASeload: unwarranted p53 signaling induced by Cas9

Mol Cell Oncol. 2020 Jul 14;7(5):1789419. doi: 10.1080/23723556.2020.1789419. eCollection 2020.

Authors

Veronica Rendo¹, Oana M Enache², Uri Ben-David³

Affiliations

¹ Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Department of Biostatistics, Duke University School of Medicine, Durham, NC, USA.
³ Department of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

We investigated the genetic and transcriptional changes associated with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated protein 9 (Cas9) expression in human cancer cell lines. For a subset of cell lines with a wild-type tumor protein TP53 (best known as p53), we detected p53 pathway activation, DNA damage accumulation and emerging p53-inactivating mutations following Cas9 introduction. We discuss the potential implications of our findings in basic and translational research.

Keywords: CRISPR; Cas9; DNA damage response; TP53 mutation; genome editing; p53 pathway.

Grants and funding

This work was supported by the Azrieli Foundation; Cancer Biology Research Center, Tel Aviv University; Israel Cancer Association, Eimert Research Grant on Solid Tumors.