Fig. 2

Fig. 2

CRISPR-Cas9 genome-wide knockout and activation screens identify novel combination partners for ATRi. a, b Upper half, CRISPR-Cas9 screen analyses using a knockout (Brunello) library in LN229 (a) and LNZ308 cells (b) using 750 nM of AZD6738. Left, 9-square plot of MAGeCK MLE results comparing Brunello sgRNA distributions from DMSO or AZD6738-treated cells to the plasmid library pool. Right, rankview plot illustrating MAGeCK MLE results comparing Brunello sgRNA distributions from AZD6738-treated cells to the corresponding DMSO control. c, d Lower half, CRISPR-Cas9 screen analyses using an activation (Calabrese) library in LN229 (c) or LNZ308 cells (d), respectively, using 1.5 µM AZD6738 for LN229 and 1.4 µM AZD6738 for LNZ308 cells. Left, 9-square plot of MAGeCK MLE results comparing Calabrese sgRNA distributions from DMSO or AZD6738-treated cells to the plasmid library pool. Right, rankview plot illustrating MAGeCK MLE results comparing Calabrese sgRNA distributions from AZD6738-treated cells to the corresponding DMSO control. The respective experimental set-up was used to prioritize genetic vulnerabilities (Brunello library) and resistance mechanisms (Calabrese library) upon ATR inhibition