Figure 1. Comparison of individual replisomes and the coupled sister replisomes.

(a) Individual replisome: Ctf4₃ connects CMG to Pol α-primase, and Pol ε binds the C-face of CMG. Three unanswered questions are represented by the three question marks: 1. What components in CMG, in addition to the CIP peptide of Sld5, interact with Ctf4₃ to maintain their stable association? 2. How does Pol α-primase interact with Ctf4₃ – on the top N-face or the bottom C-face of the Ctf4 disk? 3. Can a second Pol α-primase also occupy the third CIP-site of Ctf4₃? (b). Factory core model of two replisomes inferred from cryo-EM structures of the current report. Two CMGs bind tightly to two subunits of the Ctf4 trimer by an extensive interface formed with the Psf2 and Cdc45 subunits of CMG. One Pol α-primase occupies the third Ctf4 subunit. The single Pol α-primase connects to the C-face of Ctf4 near the split points of DNA entering the N-faces of the two CMGs. The two leading Pol ε complexes bind the C-face of CMG on the outside perimeter of the factory. See text for details.