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Mol Cell Biol. 1998 May;18(5):2748-57.

Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7.

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  • 1Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

A yeast two-hybrid screen was employed to identify human proteins that specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb) protein. Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins that comprise replication licensing factor. Full-length Rb and MCM7 form protein complexes in vitro, and the amino termini of two Rb-related proteins, p107 and p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA replication assay system. These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes.

PMID:
9566894
[PubMed - indexed for MEDLINE]
PMCID:
PMC110654
Free PMC Article

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