Reactome | CDT1-mediated loading of MCM2-7 to replication origins

CDT1-mediated loading of MCM2-7 to replication origins

Stable Identifier

R-HSA-9749320

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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CDT1-mediated loading of MCM2-7 to replication origins

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While the simultaneous binding of CDT1 to the MCM2-7 complex and CDC6, as well as the interaction between MCM2-7 and CDC6 at the origin of replication was demonstrated in human cells (Wohlschlegel et al. 2000; Wu et al. 2014), the mechanism has been studied in detail only in the budding yeast (Sun et al. 2013; Fernández-Cid et al. 2013). Based on yeast studies, CDT1 binding to the MCM2-7 complex induces a structural change in the MCM2-7 that relieves MCM2-7 autoinhibition by the C-terminus of its MCM6 subunit, enabling a direct association between MCM2-7 and CDC6 bound to the ORC(1-6) complex at the replication origin (Fernández-Cid et al. 2013). As a result, the OCCM complex is formed, which contains ORC(1-6), CDC6, CDT1 and MCM2-7 bound to the replication origin (Fernández-Cid et al. 2013, Sun et al. 2013). The binding of geminin (GMNN) to CDT1 inhibits CDT1-mediated loading of the MCM2-7 complex to replication origins (Wohlschlegel et al. 2000).

Literature References

PubMed ID	Title	Journal	Year
25231993	Geminin inhibits a late step in the formation of human pre-replicative complexes Santos, RE, Wu, M, Lu, W, Frattini, MG, Kelly, TJ	J Biol Chem	2014
11125146	Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Cvetic, C, Walter, JC, Wohlschlegel, JA, Dwyer, BT, Dutta, A, Dhar, SK	Science	2000