(A) Illustration of a hexameric helicase in the steric exclusion mode, encircling the tracking strand and excluding the non-tracking strand from the central channel. (B) CMG-forked DNA structure (PDB ID# 5U8S). Duplex DNA penetrates the zinc fingers defining the start of the central channel in the N-tier and the unwinding point is internal to the central channel (Georgescu et al., 2017). The Mcm2-7 subunits are shown in two shades of blue to highlight the N- and C-tiers. The lagging strand tail is present but not visible, indicating mobility, and is suggested to exit the central channel though a gap between two zinc fingers (dashed line) (see also panel C). (C) Illustration of CMG encountering a lagging strand block in the modified steric exclusion mode, partially encircling both strands of the duplex DNA as shown in (B). To bypass the block, CMG-DNA must isomerize to the classic steric exclusion mode in (A) or by opening of the Mcm2-7 ring during bypass (illustrated in Figure 8 of Langston and O'Donnell, 2017).