The structural evidence that S. cerevisiae CMG encircles dsDNA during unwinding is supported by recent biochemical experiments using strand specific dual streptavidin blocks that show CMG is halted by a block placed on either the non-tracking (lagging) or the tracking (leading) strand (Figure 1C) (Langston and O'Donnell, 2017). Interestingly, given a sufficiently long time S. cerevisiae CMG can proceed through the lagging strand block without displacing the streptavidin, suggesting that CMG slowly isomerizes to a classic steric exclusion mode that only encircles the tracking (leading) strand or isomerizes by ring opening to bypass the block (Langston and O'Donnell, 2017). Earlier studies in Xenopus extracts demonstrate that replisome progression is not hindered by a dual streptavidin block on the lagging strand and conclude that CMG functions in a steric exclusion mode by only encircling the leading strand (Fu et al., 2011). Considering that the zinc fingers of isolated S. cerevisiae CMG encircle dsDNA, we proposed that Xenopus extracts contain a factor that facilitates isomerization of CMG on DNA such that it can bypass blocks on the non-tracking strand (Langston and O'Donnell, 2017).