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. Author manuscript; available in PMC: 2018 May 3.
Published in final edited form as: Adv Exp Med Biol. 2017;1042:421–454. doi: 10.1007/978-981-10-6955-0_19

Fig. 19.3.

Fig. 19.3

Control of MCM2-7 loading via the UPS. The APC/CCdh1 ligase promotes MCM2-7 loading in late M and in G1 by degrading Geminin. However, APC/CCdh1 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, SCFSKP2 and CRL4CDT2 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 (SCFCyclin 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