We have shown that a stoichiometric CMG-Mcm10 complex can be reconstituted and isolated (Figure 2D and Figure 2—figure supplements 3–5) and that Mcm10 greatly stimulates CMG unwinding and processivity (Figures 2 and 3). Interestingly, the effect of Mcm10 on fork progression per se is relatively insignificant in the absence of blocks (Figure 4). Notably, we find that Mcm10 enables CMG and the replisome to bypass lagging strand blocks that otherwise bring unwinding and leading strand synthesis to a halt (Figures 5 and 6). The function of Mcm10 in facilitating replisome bypass of lagging strand blocks is consistent with genetic studies showing that Mcm10 deficiency leads to genome instability and increased dependence on post-replication and recombinational repair pathways to maintain viability (Araki et al., 2003; Lee et al., 2010).