The replication of cellular DNA requires use of a helicase to separate the interwound strands. The replicative helicase in all domains of life is a circular hexamer. There are four superfamilies of hexameric helicases, SF3-6, that assort into two main groups, the bacterial helicases (SF4,5) that have ATP sites derived from the RecA fold and the eukaryotic/archaeal helicases (SF3,6) that have ATP sites derived from the AAA+ fold (Singleton et al., 2007). In all cases, the subunits of hexameric helicases are composed of at least two major domains, giving them the appearance of two stacked rings, an N-tier ring and C-tier ring; the motors are contained in the C-tier ring. The RecA based bacterial helicases track 5’−3’ on DNA with the C-tier motors leading the N-tier, as determined by crystal structures of bacterial Rho (SF5) and DnaB (SF4) complexed with ssDNA, while structures of eukaryotic bovine papilloma virus E1 (SF3) and S. cerevisiae CMG (SF6) with DNA show that these helicases track 3’−5’ with the N-tier ahead of the C-tier (Enemark and Joshua-Tor, 2006; Georgescu et al., 2017; Itsathitphaisarn et al., 2012; Thomsen and Berger, 2009).