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PMID:21196493

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Citation

Nishiyama, A, Frappier, L and Méchali, M (2011) MCM-BP regulates unloading of the MCM2-7 helicase in late S phase. Genes Dev. 25:165-75

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.

Links

PubMed PMC3022262 Online version:10.1101/gad.614411

Keywords

Animals; Carrier Proteins/metabolism; Cell Cycle Proteins/metabolism; Cell Nucleus/metabolism; Chromatin/metabolism; Chromosomal Proteins, Non-Histone/metabolism; DNA Helicases/metabolism; Gene Silencing; HeLa Cells; Humans; Protein Binding; Protein Transport; RNA, Small Interfering/metabolism; S Phase/physiology; Xenopus Proteins/metabolism

Significance

Annotations

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

XENLA:MCMBP

colocalizes_with

GO:0042555: MCM complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:MCMBP

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:MCMBP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91876

F

Seeded From UniProt

complete

XENLA:MCMBP

involved_in

GO:0006261: DNA-dependent DNA replication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:MCM7A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q7ZYP6

F

Seeded From UniProt

complete

HUMAN:MCMBP

involved_in

GO:0006261: DNA-dependent DNA replication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MCMBP

involved_in

GO:0006261: DNA-dependent DNA replication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

happens_during:(GO:0000084)

Seeded From UniProt

complete


See also

References

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