Fig. 1: Loss of EIF2A sensitizes cells to WEE1 inhibition.

a Experimental setup of the viral insertional mutagenesis screen in (b). b Sense/total insertion ratios from mutagenesis screens performed in HAP1 cells treated with AZD1775 or DMSO. Genes with significantly less sense insertions in AZD1775-treated cells are indicated. c Schematic representation of high-ranking gene mutations causing sensitization to WEE1i. d Pathway enrichment analysis, depicting the most highly enriched pathways involved in sensitization to WEE1i. e, f Dose-response curve of AZD1775 in control RPE1 TP53^KO and RPE1 TP53^KO EIF2A^KO cells (e) and OVCAR3, OVCAR3 EIF2A^KO #1 and OVCAR3 EIF2A^KO #2 cells (f). Cells were treated for 5 days and cellular viability was measured by MTT conversion. Data represent mean ± standard deviation (SD) (n = 3). g Immunofluorescence microscopy analysis of γH2AX in control RPE1 TP53^KO and EIF2A^KO cells treated with AZD1775 (500 nM) for 24 h. Mean foci intensity per cell is plotted. Medians of n = 218, 212, 228 or 206 cells, respectively, measured across 3 independent experiments. Paired t-test (two-sided) of medians, p ≤ 0.05 was considered significant. h scEdU-seq maximum normalized log counts are plotted for control RPE1 TP53^KO and RPE1 TP53^KO EIF2A^KO cells, ranked according to S-phase progression (y-axis) and binned per 400 kb (x-axis). A 40 megabase region of chromosome 2 is shown. All replicates are biological replicates unless indicated otherwise. Source data are provided as a Source data file.