Extended Data Fig. 9: Related to Fig. 3. FANCM:SMARCAL1-deficient cells are highly sensitive to hydroxyurea or Olaparib.
From: Comprehensive interrogation of synthetic lethality in the DNA damage response
a, Left: schematic representation of the drug sensitivity assay. Right: dual-color flow cytometry survival curves for cells expressing the indicated sgRNAs and treated with mitomycin C (5 nM, 24 h; n = 3 technical replicates), hydroxyurea (2 mM, 24 h; n = 2 experimental replicates), or Olaparib (2 µM, chronic; n = 3 technical replicates). Cell population ratios were normalized to those of corresponding untreated cells. A full stress sensitization panel can be found in (b). b, Cells were treated with genotoxic agents (APH, aphidicolin; PDS, pyridostatin; ETO, etoposide; CPT, camptothecin) 96 hrs after transduction with the indicated sgRNAs. Concentrations and treatment durations are indicated above each panel. Cells were re-analysed by FACS 7 days later. Cell population ratios were normalized to those of corresponding untreated cells. Three technical replicates are shown. Error bars represent mean ± s.d. c, Survival curves of RPE-1 TP53 KO cells transduced with sgRNAs targeting FANCM and SMARCAL1 and nucleofected with a cDNA encoding either wild-type (WT) or R-loop-binding defective (WKKD) RNase H1.
