Fig. 6: DNA damage induces markers of proteotoxic stress.

Consistent with the idea that these errors result in misfolded proteins, these cells displayed markers of proteotoxic stress, including upregulated autophagy genes (A), heat shock proteins (B) and proteins implicated in the ubiquitin-proteasome system (C). Depicted in figure A and C is the average percentage change for all autophagy and ubiquitination-related genes identified by bulk RNA-seq. The genes depicted in B have been separated from several heat shock proteins that displayed unusually large increases in transcript levels (Supplementary Fig. 9, Supplementary Table 4). n = 3 biological replicates, for autophagy P < 0.0001, for heat-shock proteins P = 0.0016 at 6 h and P = 0.0287 at 24 h. For ubiquitin P < 0.0001. *P < 0.05, **P < 0.01, ****P < 0.0001 according to a two-tailed paired t-test with Welch’s correction. D. Heat map of autophagy genes detected in WT and mutant cells. E Error spectrum of human cells after transformation with plasmid that carries an editing target, the gRNA required to edit the target, and the editing enzyme. If the editing enzyme is present, large numbers of A to I editing events (A to G errors) were observed. n = 2 biological replicates. F Percentage of editing events that generate mRNAs with various mutant:WT ratios. Data are presented as mean values ± SEM. Source data are provided as a Source Data file.