FIGURE 1 from De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression

Multiple CRISPR KO screens identify nucleotide metabolism genes that are selectively depleted in p16/CDKN2Alow cells. A, Schematic of our CRISPR screens. p16/Cdkn2a wildtype cells were infected with lentiviruses expressing shGFP control (shCont), shp16 (human), or shCdkn2a (mouse). Human and mouse isogenic cell pairs were infected with nucleotide-focused or whole metabolism-focused CRISPR gRNA libraries, respectively, at an MOI of <0.3. After 14 days in culture, gDNA was harvested and sequenced. Analysis of genes included in the “nucleotide metabolism signature” (Supplementary Table S1) identified multiple genes that are negatively enriched in shp16/shCdkn2a vs. shCont in human SKMEL28 (B) and mouse Yumm5.2 (C) melanoma cells. Raw data can be found in Supplementary Tables S3 and S4. D, Comparison of datasets and list of 31 common genes negatively enriched (log₂ fold change <0) in the indicated analyses.