Fig. 1.

Establishment of DDX11 KO in cancer cell lines and identification of synthetic lethal drugs (A) Cell viability assay of ovarian cancer cell line UWB1.289 + BRCA1 transfected with siCtrl and siDDX11. Cells were treated with olaparib and cisplatin with the indicated drug concentrations (n = 3). (Right) Corresponding Western blot. Error bars show average ± SEM. (B) Schematic representation of DDX11 genomic locus, targeted by the CRISPR-paired guide RNAs at exons 7 and 9 to establish KO in HeLa and U2OS cell lines. (C) Western blot analysis of DDX11 in HeLa and U2OS cell lines to assess DDX11 targeting with CRISPR-paired guide RNAs. (D) Schematic representation of synthetic lethal drug screen (Food and Drug Administration [FDA]–approved drugs) in HeLa Ctrl and DDX11 KO cells in which cell viability was determined 72 h after drug treatment with 64 FDA-approved drugs at different concentrations using CellTiter-Glo (n = 2). (E) Colony formation assay of HeLa Ctrl and DDX11 KO cells exposed to olaparib (n = 2), cisplatin (n = 3), and ATRi AZD6738 (n = 3) with the indicated drug concentrations. Colonies were stained with crystal violet after 10 to 15 d of incubation. For cisplatin, after 1 h of acute treatment, cells were allowed to grow in normal media. Error bars show average ± SEM.