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

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

Stable Identifier

R-HSA-68712

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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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, Lee, E, Kirschner, MW	Genes Dev	2001
17485488	Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C Di Fiore, B, Pines, J	J Cell Biol	2007
17234884	The APC/C inhibitor, Emi1, is essential for prevention of rereplication Machida, YJ, Dutta, A	Genes Dev	2007