Fig. 19.3.

Control of MCM2-7 loading via the UPS. The APC/C^Cdh1 ligase promotes MCM2-7 loading in late M and in G1 by degrading Geminin. However, APC/C^Cdh1 also appears to limit the abundance of certain licensing factors like Drosophila ORC1 and mammalian CDC6 in G1, narrowing to late M-phase the window in the cell cycle when there is enough ORC, CDC6, and active CDT1 available to load MCM2-7 on origins. The E3 ubiquitin ligases, SCF^SKP2 and CRL4^CDT2 limit the abundance of key proteins involved in MCM2-7 loading (pre-RC assembly) in the S-, G2-, and early M-phases of the cell cycle. The SCF ubiquitin ligase also utilizes the substrate recognition subunit cyclin F (SCF^{Cyclin F}; red dashed lines) to suppress origin relicensing by promoting the ubiquitylation and degradation of CDC6 in late G2- and early M-phase of the cell cycle