Extended Data Fig. 7.

a, Processing pipeline for the hSH structure that was obtained from the human MCM loading reaction in the presence of ATP. b, Schematic representation of protein–protein interactions in hMO*, yMO, yMCM–Cdt1, hOCCM and yOCCM. In hMO*, the N-terminal cyclin box domain interacts with MCM2, MCM6 and ORC4, while the C-terminal cyclin box binds MCM6, MCM4 and ORC5. The resolution of the ORC3 specific insertion is limited. Thus, we cannot see the C-terminal alpha helix of ORC6 binding ORC3, which has been previously seen in the yeast and Drosophila ORC structures. The N-terminal cyclin box domain of yeast Orc6 binds similarly to Mcm2 and Mcm6, but it does not interact with Orc4. The C-terminal cyclin box domain of yeast Orc6 establishes contacts with Orc2 and Orc3. The C-terminal alpha helix of Orc6 also contacts Mcm5 and thereby bridges the Mcm2–Mcm5 DNA entry gate. In MCM–Cdt1, hOCCM and yOCCM, CDT1 establishes interactions with the same MCM subunits that are contacted by ORC6 in hMO*. In this context, the MCM2-MCM5 gate appears accessible.