Proposed model of Mcm10 mediated isomerization of CMG-DNA at a replication fork. Left, CMG encounters an impediment on the DNA but cannot pass it because it surrounds dsDNA in the N-terminal tier of Mcm2-7 (as in Figure 1C); middle, Mcm10 binds to the forked junction and to the N-terminal tier of CMG, releasing CMG’s grip on the duplex DNA and placing CMG in a steric exclusion mode encircling ssDNA (as in Figure 1A); right, with the lagging strand freed from the interior of the Mcm2-7 ring, CMG can bypass the impediment on the DNA and proceed. Alternative isomerization reactions that could also accomplish bypass of a bulky block are discussed in the text.