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PMID:18657502

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Citation

Lutzmann, M and Méchali, M (2008) MCM9 binds Cdt1 and is required for the assembly of prereplication complexes. Mol. Cell 31:190-200

Abstract

Prereplication complexes (pre-RCs) define potential origins of DNA replication and allow the recruitment of the replicative DNA helicase MCM2-7. Here, we characterize MCM9, a member of the MCM2-8 family. We demonstrate that MCM9 binds to chromatin in an ORC-dependent manner and is required for the recruitment of the MCM2-7 helicase onto chromatin. Its depletion leads to a block in pre-RC assembly, as well as DNA replication inhibition. We show that MCM9 forms a stable complex with the licensing factor Cdt1, preventing an excess of geminin on chromatin during the licensing reaction. Our data suggest that MCM9 is an essential activating linker between Cdt1 and the MCM2-7 complex, required for loading the MCM2-7 helicase onto DNA replication origins. Thus, Cdt1, with its two opposing regulatory binding factors MCM9 and geminin, appears to be a major platform on the pre-RC to integrate cell-cycle signals.

Links

PubMed Online version:10.1016/j.molcel.2008.07.001

Keywords

Animals; Cell Cycle Proteins/metabolism; Chromatin/metabolism; DNA Replication; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Gene Deletion; HeLa Cells; Humans; Molecular Weight; Origin Recognition Complex/metabolism; Protein Binding; Vertebrates/metabolism; Xenopus; Xenopus Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

XENLA:MCM9

GO:0031490: chromatin DNA binding

ECO:0000314:

F

Figure 3A

complete

XENLA:MCM9

GO:0006267: pre-replicative complex assembly

ECO:0000314:

P

Figure 2

complete

XENLA:MCM9

GO:0005515: protein binding

ECO:0000021:

UniProtKB:Q9I9A7


F

Co-Immunoprecipitates from Figure 4C

complete

XENLA:CDT1

GO:0005515: protein binding

ECO:0000021:

UniProtKB:Q6NRM6


F

Co-Immunoprecipitates from Figure 4C

complete


See also

References

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