Fig. 3: ATM loss-of-function through genetic knockout or small molecule inhibition leads to increased 1-bp insertion frequency.

a Bar chart showing the fraction of 1bp-insertion mutations among edited reads at three GFP-targeting gRNA sites in Atm or control knockout mESCs (N = 2 biologically independent samples). b Bar chart exhibiting the edited fraction of all mapped reads for each of the conditions described in a, respectively. c Boxplot exhibiting the fraction of 1-bp insertions observed in mESCs for each site of the 48-site library in the presence of known ATM inhibitors or DMSO (N = 3 biologically independent samples). d Boxplot exhibiting the editing frequency observed for each site depicted in c, respectively. P values were calculated using a one-way ANOVA with Tukey HSD).**p < 0.01, and ***p < 0.001. Boxplot statistics for 1-bp insertion fraction with AZ32: minima = 0.401, lower whisker bound = 0.447, lower box bound = 1.210, center = 1.423, upper box bound = 1.722, and upper whisker bound = 2.350. Boxplot statistics for 1-bp insertion fraction with AZD1390: minima = 0.316, lower whisker bound = 0.316, lower box bound = 1.268, center = 1.763, upper box bound = 2.261, upper whisker bound = 3.191, maxima = 3.191. Boxplot statistics for 1-bp insertion fraction with CPP466: minima = 0.743, lower whisker bound = 0.795, lower box bound = 1.286, center = 1.421, upper box bound = 1.662, and upper whisker bound = 2.074. Boxplot statistics for 1-bp insertion fraction with DMSO: minima = 0.837, lower whisker bound = 0.837, lower box bound = 0.947, center = 1.011, upper box bound = 1.060, and upper whisker bound = 1.163. Boxplot statistics for total edited fraction with AZ32: minima = 0.022, lower whisker bound = 0.022, lower box bound = 0.040, center = 0.053, upper box bound = 0.066, and upper whisker bound = 0.090. Boxplot statistics for total edited fraction with AZD1390: minima = 0.011, lower whisker bound = 0.011, lower box bound = 0.015, center = 0.021, upper box bound = 0.027, upper whisker bound = 0.032, and maxima = 0.032. Boxplot statistics for total edited fraction with CPP466: minima = 0.031, lower whisker bound = 0.031, lower box bound = 0.061, center = 0.077, upper box bound = 0.113, and upper whisker bound = 0.160. Boxplot statistics for total edited fraction with DMSO: minima = 0.036, lower whisker bound = 0.036, lower box bound = 0.046, center = 0.059, upper box bound = 0.075, upper whisker bound = 0.094, and maxima = 0.094.