Together, the results of Figures 2 and 3 show that Mcm10 strongly stimulates CMG unwinding, yet the experiments of Figure 4 indicate that Mcm10 is not essential for normal replisome progression in vitro, particularly in the presence of the MTC complex. To explain these apparently conflicting results, we hypothesized that Mcm10 is required for replisome progression in particular circumstances, for example when CMG is hindered by DNA-bound proteins or other structural impediments on DNA. Indeed, Mcm10 is required for efficient initiation of DNA unwinding at an origin, a situation in which the two CMG complexes block one another's progression because they must pass each other in order to establish two bidirectional forks (see Discussion) (Georgescu et al., 2017).