title: MCM-BP regulates unloading of the MCM2-7 helicase in late S phase.
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.
authors.affiliation: Institute of Human Genetics, CNRS, 34396 Montpellier, France.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Lori
authors.initials: L
authors.lastname: Frappier
authors.forename: Marcel
authors.initials: M
authors.lastname: Méchali
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C555939:MCMBP protein, Xenopus; D034741:RNA, Small Interfering; D029867:Xenopus Proteins; D004265:DNA Helicases; C102186:Mcm2 protein, Xenopus; D064111:Minichromosome Maintenance Complex Component 2