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Human Interaction Network Ontology
| Preferred Name | Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC) | |
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| Definitions |
Genetic studies in S. cerevisiae indicate that wild-type Cdc6 function is required for correctly timed loading of Mcm2-7 onto ORC. Biochemical studies indicate that the human and Xenopus Cdc6 proteins likewise are required for Mcm2-7 loading, and that they are ATPase switches. Specifically, Cdc6 may function as a clamp loader, assembling Mcm2-7 onto DNA in an ATP-dependent reaction. All known Cdc6 proteins have the Walker A and Walker B sequence motifs characteristic of the AAA+ superfamily of ATPases. As expected for an AAA+ protein, human Cdc6 binds and slowly hydrolyzes ATP in vitro. ATP hydrolysis was disrupted by mutations of the Walker B motif, while both binding and hydrolysis were disrupted by Walker A mutations. Microinjection of either mutant protein into HeLa cells blocked their progression through S phase. Both wild-type and mutant proteins can dimerize in vitro, and studies with Xenopus egg extracts suggest that Cdc6 functions in vivo as a dimer or larger multimer. In Xenopus extracts depleted of Cdc6 and reconstituted with either mutant protein, recruitment of Mcm2-7 to chromatin failed. |
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http://purl.obolibrary.org/obo/HINO_0014853 |
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| comment |
Genetic studies in S. cerevisiae indicate that wild-type Cdc6 function is required for correctly timed loading of Mcm2-7 onto ORC. Biochemical studies indicate that the human and Xenopus Cdc6 proteins likewise are required for Mcm2-7 loading, and that they are ATPase switches. Specifically, Cdc6 may function as a clamp loader, assembling Mcm2-7 onto DNA in an ATP-dependent reaction. All known Cdc6 proteins have the Walker A and Walker B sequence motifs characteristic of the AAA+ superfamily of ATPases. As expected for an AAA+ protein, human Cdc6 binds and slowly hydrolyzes ATP in vitro. ATP hydrolysis was disrupted by mutations of the Walker B motif, while both binding and hydrolysis were disrupted by Walker A mutations. Microinjection of either mutant protein into HeLa cells blocked their progression through S phase. Both wild-type and mutant proteins can dimerize in vitro, and studies with Xenopus egg extracts suggest that Cdc6 functions in vivo as a dimer or larger multimer. In Xenopus extracts depleted of Cdc6 and reconstituted with either mutant protein, recruitment of Mcm2-7 to chromatin failed.
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| definition source |
Pubmed9407030 Reactome, http://www.reactome.org Pubmed10801458 Pubmed11950940 Pubmed11006548 Pubmed10436018
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Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC)
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| prefixIRI |
HINO:0014853
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Mcm2-7 associates with the Cdt1:CDC6:ORC:origin complex, forming the pre-replicative complex (preRC)
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| seeAlso |
ReactomeREACT_1770 Reactome Database ID Release 4368849
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