Fig. 1
Genome-wide CRISPR-Cas9 and insertional mutagenesis screens identify the BLM complex as a synthetic viable interaction for FANCC. a Workflow for the identification of genetic synthetic viable interactions for ∆FANCC cells following MMC exposure by two parallel genome-wide approaches: CRISPR-Cas9 and insertional mutagenesis. b Viability-inducing genes identified using a genome scale CRISPR knock-out (GeCKO) library in ∆FANCC cells treated with MMC, compared to untreated WT cells are shown in red, and include members of the BLM complex, FANCM and NQO1. Each dot represents the average score of the six guide RNAs (gRNAs) per gene. c Viability-inducing genes identified using gene-trap insertional mutagenesis in ∆FANCC cells treated with MMC, compared to untreated WT cells. Members of the BLM complex and NQO1 are labeled. For robust identification of enriched genes in b, c, hit selection was performed in two steps. First, each data set was partitioned into two groups, defining the hit-group as data points with p < 0.001 and fold-change >21.5. In a second step, hit selection was optimized using linear discriminant function analysis. d–h Indicated cell lines were exposed to MMC for 4 days and cellular survival was assessed by CellTiter-Glo. Means and S.E.M. of biological triplicates are plotted
