(A) In eukaryotic cells under normal conditions origin licensing starts with the ORC1-ORC5 subunits of ORC partially encircling the origin of replication. CDC6 (dark gray) then binds to ORC1 (red) and ORC2 (green) to complete a protein ring around the DNA. The ORC-CDC6 complex interacts with a ring-shaped MCM2-7 helicase (light gray) such that the helicase (which is bound to the CDT1 protein; black) encircles the adjacent DNA. (B) A model for origin licensing by an origin recognition complex that lacks ORC1 or ORC2. This partial ORC still binds to DNA, and CDC6 binds to either ORC1 or ORC2 to form a five-subunit partial ring around the DNA. This new complex retains the ability to recruit MCM2-7 and CDT1. (C) A model for how origin licensing could occur in the absence of the origin recognition complex. CDC6 either directly (left) or indirectly (by binding a different DNA-bound protein; right) binds to DNA and recruits MCM2-7 and CDT1 to the origin of replication.