Fig. 6: Effect of RAD18 on TMZ-induced mutagenesis.

a Experimental workflow of experiments to define impact of RAD18 and MMR on TMZ-induced mutagenesis. b Bar charts showing numbers of total SNV arising de novo following TMZ treatment over the course of 20 PD in cell lines differing with respect to RAD18 and MMR status. c, d Bar charts showing numbers of each individual SNV arising de novo following TMZ treatment over 20 PD in MLH1+/+ (c) and MHL1−/− (d) cells. Pattern I (O6mG-induced) and Pattern II (N3mA- and N7mG-induced) SNVs are indicated; NS no significance. e Stacked bar-chart showing contribution of individual COSMIC mutation signatures to the overall mutational patterns of U373 clones obtained from different treatment groups. f Bar chart showing effect of RAD18 and MLH1 status on mutational Signature 11 counts in clones of TMZ-treated U373 cells. NS, no significance. All data points represent mean ± SD of 6 single clone samples; p values were determined by two-sided t test (b, c, d) and two-sided t test with Tukey HSD adjust (f). (a) was created with BioRender.com.