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. 2010 Apr 26;38(16):5409–5418. doi: 10.1093/nar/gkq262

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© The Author(s) 2010. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 7. — Outline of the observations leading to the inhibition of DNA replication by deregulated Cdc6. (A) Cdc6 is targeted to origin after chromatin binding of ORC. (B) Mcm2–7 is recruited to chromatin by Cdt1. (C) After Mcm2–7 has been loaded onto chromatin (licensing), Cdc6 is destabilized from chromatin. (D) Origin firing occurs by Cdc7 (DDK)-dependent phosphorylation of Mcm2–7 in concert with Cdk2 kinase activity. (E) When Cdc6 is deregulated resulting in insufficient removal from chromatin after licensing, DNA replication is arrested after chromatin loading of DDK. (F) Persisting Cdc6 on chromatin after origin licensing prevents Cdc7-dependent phosphorylation of Mcm2–7 thereby blocking further steps.