Figure 5.
MMEJ Has Slower Repair Kinetics Than C-NHEJ
(A) Kinetic model of Cas9-induced DSB repair assuming that each type of indel is generated with a specific repair rate.
(B) +1 insertion and −7 deletion accumulation in a representative time series. Dashed lines show a Gompertz sigmoid fit.
(C) Same measurements as in (B) with the multi-indel ODE model fit (solid lines) for the +1 (top) and −7 (bottom) indels.
(D) Cartoon representation of hypothesized time dependency of the k+1 and k−7 rates added to the fitted model in (E).
(E) Time-dependent ODE model fit of the +1 insertion (top) and −7 deletion (bottom) as proposed in (D).
(F) Rate constants without (black) and with (gray) NU7441. The total mutagenic repair rate is represented by km; rate constant for the +1 insertion is k+1 and rate constants for the −7 deletion are k−7,t = 0hr and k−7,t = 60hr at the start and end of the time series, respectively. n indicates the number of time series. Asterisks indicate p values according to Wilcoxon test: ∗p < 0.05; ∗∗p < 0.005; ∗∗∗p < 0.0005.
(G) Broken fraction measurements in presence of NU7441 of 2 independent time series, similar to Figures 3B and 3C.