CDT1 binds geminin

Stable Identifier
R-HSA-69299
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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CDT1 binds geminin
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Geminin (GMNN) tightly binds to CDT1 and inhibits CDT1-mediated loading of the MCM2-7 complex to replication origins. During cell cycle, CDT1 is present only in G1 and S phases, while geminin is present in S and G2 phases. Geminin is thought to prevent inappropriate firing of replication origins during the G2 phase in multicellular eukaryotes (Wohlschlegel et al. 2000).

It has also been proposed that, instead of inhibiting CDT1-mediated loading of the MCM2-7 complex to ORC and CDC6 at the origins of replication, geminin binds to the pre-replicative complex and inhibits its transition to a state competent for initiation of DNA replication (Wu et al. 2014). The study by Wu et al. 2014, however, used recombinant, overexpressed human proteins, and did not take into account cell-cycle regulated expression of CDT1, CDC6 and geminin.
Literature References
PubMed ID Title Journal Year
25231993 Geminin inhibits a late step in the formation of human pre-replicative complexes

Wu, M, Lu, W, Santos, RE, Frattini, MG, Kelly, TJ

J Biol Chem 2014
11125146 Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.

Wohlschlegel, JA, Dwyer, BT, Dhar, SK, Cvetic, C, Walter, JC, Dutta, A

Science 2000
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