The geminin component of geminin:Cdt1 complexes is ubiquitinated, releasing Cdt1

Stable Identifier
R-HSA-68712
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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From the end of anaphase and throughout G1, the Cdh1 (FZR1) containing anaphase-promoting complex (APC/C:Cdh1) ubiquitinates geminin (GMNN), targeting it for degradation and enabling release of CDT1 and the subsequent association of CDT1 with the replication origins.The presence of an APC destruction box in geminin and its APC/C-mediated ubiquitination and degradation was first demonstrated in Xenopus egg extracts (McGarry and Kirschner 1998) and was later confirmed in human cells, where it was shown to largely depend on Cdh1 and not Cdc20 component of the APC/C (Pfleger et al. 2001; Di Fiore and Pines 2007; Machida and Dutta 2007). Emi1 (FBXO5) mediated inhibition of the APC/C:Cdh1 complex in S and G2 phases is needed for stabilization of geminin and prevention of re-replication (Di Fiore and Pines 2007; Machida and Dutta 2007).

Literature References
PubMed ID Title Journal Year
9635433 Geminin, an inhibitor of DNA replication, is degraded during mitosis.

McGarry, TJ, Kirschner, MW

Cell 1998
11562349 Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex

Pfleger, CM, Kirschner, MW, Lee, E

Genes Dev 2001
17485488 Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C

Pines, J, Di Fiore, B

J Cell Biol 2007
17234884 The APC/C inhibitor, Emi1, is essential for prevention of rereplication

Dutta, A, Machida, YJ

Genes Dev 2007
Participants
Participates
Catalyst Activity

ubiquitin-protein transferase activity of phospho-Cdh1:phospho-APC/C complex [nucleoplasm]

Orthologous Events
Reviewed
Created
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