In contrast, S. cerevisiae CMG is inhibited by a block on either the non-tracking strand or the tracking strand (Langston and O'Donnell, 2017), consistent with the CMG-forked DNA structure showing that CMG encircles both strands of the forked junction (see Figure 1B–C) (Georgescu et al., 2017). However, when given sufficient time, the bulk of the CMGs that progress past the lagging strand block leave streptavidin attached to DNA and thus slowly isomerize on DNA to bypass the block without displacing it (Langston and O'Donnell, 2017). Isomerization for bypass could be achieved by CMG encircling only the leading strand or the Mcm2-7 ring within CMG may crack open for bypass, as detailed later in the Discussion.