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Genes Dev. 2011 Jan 15;25(2):165-75. doi: 10.1101/gad.614411. Epub 2010 Dec 31.

MCM-BP regulates unloading of the MCM2-7 helicase in late S phase.

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  • 1Institute of Human Genetics, CNRS, 34396 Montpellier, France.

Abstract

Origins of DNA replication are licensed by recruiting MCM2-7 to assemble the prereplicative complex (pre-RC). How MCM2-7 is inactivated or removed from chromatin at the end of S phase is still unclear. Here, we show that MCM-BP can disassemble the MCM2-7 complex and might function as an unloader of MCM2-7 from chromatin. In Xenopus egg extracts, MCM-BP exists in a stable complex with MCM7, but is not associated with the MCM2-7 hexameric complex. MCM-BP accumulates in nuclei in late S phase, well after the loading of MCM2-7 onto chromatin. MCM-BP immunodepletion in Xenopus egg extracts inhibits replication-dependent MCM dissociation without affecting pre-RC formation and DNA replication. When excess MCM-BP is incubated with Xenopus egg extracts or immunopurified MCM2-7, it binds to MCM proteins and promotes disassembly of the MCM2-7 complex. Recombinant MCM-BP also releases MCM2-7 from isolated late-S-phase chromatin, but this activity is abolished when DNA replication is blocked. MCM-BP silencing in human cells also delays MCM dissociation in late S phase. We propose that MCM-BP plays a key role in the mechanism by which pre-RC is cleared from replicated DNA in vertebrate cells.

PMID:
21196493
[PubMed - indexed for MEDLINE]
PMCID:
PMC3022262
Free PMC Article
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