Journal: Nucleic Acids Research
Article Title: Genome-wide CRISPR screens identify the EXO1-CAF-1 pathway suppressing R-loop-associated DNA damage
doi: 10.1093/nar/gkag226
Figure Lengend Snippet: Co-depletion of EXO1 and CHAF1A reduces cellular viability. ( A, C, E ). Volcano plots showing the results of genome-wide CRISPR knockout screens to identify EXO1 synthetic lethality interactions. Genes targeted by the library are presented based on their impact on the viability of EXO1 KO#1 compared to WT cells ( A ), EXO1 KO#3 compared to WT cells ( C ), and as control, EXO1 KO#1 compared to EXO1 KO#3 cells ( E ). Genes are plotted by the −log 10 of their respective negative and positive P -values and associated log 2 Fold Change values. The hit chosen for validation, namely CHAF1A, is indicated. ( B, D, F ) Scatterplots showing the results of genome-wide CRISPR knockout screens to identify EXO1 synthetic lethality interactions. Genes targeted by the library are plotted based on their impact on the viability of EXO1 KO#1 compared to WT cells ( B ), EXO1 KO#3 compared to WT cells ( D ), and as control, EXO1 KO#1 compared to EXO1 KO#3 cells ( F ). The hit chosen for validation, namely CHAF1A, is indicated. ( G ) Table showing the ranks in the synthetic lethality screens, and the biological roles of CHAF1A. ( H, I ) Clonogenic survival assays showing that siRNA ( H ) and sgRNA ( I ) depletion of CHAF1A reduces the viability of EXO1-knockout cells compared to WT HeLa cells. Clonogenic survival is presented normalized to WT control cells. The average of three independent experiments, with standard deviations indicated as error bars, is shown. Asterisks indicate statistical significance ( t -test unpaired).
Article Snippet: For CRISPR knockout screens, the Brunello Human CRISPR knockout pooled lentiviral library (Addgene 73179) was used [ ].
Techniques: Genome Wide, CRISPR, Knock-Out, Control, Biomarker Discovery