Fig. 1.

Identification of Polq synthetic lethal (PolqSL) genes by CRISPR screening. a Schematic of the CRISPR genetic screen to identify PolqSL genes. b Violin plot of Gene Abundance Change Scores (Log₂) for DDR gene-targeting sgRNAs (red) and non-targeting control sgRNAs (blue) in Polq^−/− and Polq^hPOLQ MEFs, relative to WT MEFs. c Volcano plot of Gene Abundance Change Scores (Polq^−/− versus Polq^hPOLQ) and -Log₁₀ p-value of the Kolmogorov-Smirnov test for DDR gene-targeting sgRNAs relative to non-targeting control sgRNAs. Thresholds for statistical significance are indicated by dashed lines (see “Methods” for details). Genes with statistically significant (Blue dots) and non-significant (Gray dots) Gene Abundance Changes Scores are indicated. Genes with red/purple triangles are further validated in Fig. 1d. d Relative cell survival measured by colony forming efficiency of WT or Polq^−/− cells transduced with a lentivirus containing Cas9 and control sgRNA (sgCtrl) or DDR gene-targeting sgRNAs. Data shown are the mean ± SEM (n = 3 biological replicates). Significance determined using an unpaired, two-tailed t-test (*p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001). e Functional classification of PolqSL genes identified in our CRISPR screen depicted as a Euler diagram