Previous reports have solved the structure of the internal DNA binding region of Xenopus Mcm10 and documented that the internal region has two DNA binding elements, an OB fold and a zinc finger, that allow it to bind ssDNA and/or dsDNA (Du et al., 2012; Robertson et al., 2008; Warren et al., 2008). Following the internal DNA binding region is a C-terminal region that forms the main interaction site to Mcms (Douglas and Diffley, 2016; Lõoke et al., 2017; Quan et al., 2015). Furthermore, Mcm10 appears to bind to the N-tier region of the CMG complex that faces the forked junction (Figure 1B), as recent studies show that interaction of Mcm10 with Mcm2-7 is mediated primarily through an interaction with a conserved domain in the N-terminal region of the Mcm2 subunit (Lõoke et al., 2017). Consistent with these known properties of Mcm10, we propose in Figure 7 that, upon encountering a lagging strand block, Mcm10 binds at the N-tier of CMG and also binds DNA at the fork. This places Mcm10 between CMG and the forked junction such that duplex DNA no longer enters the zinc fingers that line the top of the central channel of CMG. In this configuration, Mcm10 isomerizes CMG to a steric exclusion mode where it is capable of bypassing blocks on the non-tracking strand as observed with other hexameric helicases and with the complete replisome in the Xenopus extract system (Fu et al., 2011). Two alternative isomerization reactions that would also facilitate lagging strand block bypass without displacement include one in which Mcm10 cracks open the N-tier of the Mcm2-7 ring of CMG, bypasses the block, and recloses the N-tier. Similarly, Mcm10 might enable opening of both the N- and C-tiers, either simultaneously or in succession, to bypass the blocks. These alternative isomerization reactions are described in detail in (Figure 8 of Langston et al., 2017).