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Cell Cycle
2018 Jan 01;174:492-505. doi: 10.1080/15384101.2017.1415681.
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MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.
Mimura S
,
Kubota Y
,
Takisawa H
.
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The minichromosome maintenance (MCM) complex, consisting of six subunits, Mcm2-7, is loaded onto replication origins through loading factors (origin recognition complex [ORC], Cdc6, and Cdt1) and forms an MCM double hexamer that licenses the initiation of DNA replication. Previous studies with Xenopus egg extracts showed that loading factors, especially Cdc6, dissociate from chromatin on MCM loading, but the molecular mechanism and physiological significance remain largely unknown. Using a cell-free system for MCM loading onto plasmid DNA in Xenopus egg extracts, we found that MCM loaded onto DNA prevents DNA binding of the loading factors ORC, Cdc6, and Cdt1. We further report that a peptide of the C-terminal region of MCM3 (MCM3-C), previously implicated in the initial association with ORC/Cdc6 in budding yeast, prevents ORC/Cdc6/Cdt1 binding to DNA in the absence of MCM loading. ATP-γ-S suppresses inhibitory activities of both the MCM loaded onto DNA and the MCM3-C peptide. Other soluble factors in the extract, but neither MCM nor Cdt1, are required for the activity. Conservation of the amino acid sequences of MCM3-C and its activity in vertebrates implies a novel negative autoregulatory mechanism that interferes with MCM loading in the vicinity of licensed origins to ensure proper origin licensing.
Abid Ali,
The MCM Helicase Motor of the Eukaryotic Replisome.
2016, Pubmed
Abid Ali,
The MCM Helicase Motor of the Eukaryotic Replisome.
2016,
Pubmed
Aparicio,
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
1997,
Pubmed
Bell,
DNA replication in eukaryotic cells.
2002,
Pubmed
Blow,
How dormant origins promote complete genome replication.
2011,
Pubmed
Bowers,
ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication.
2004,
Pubmed
Burkhart,
Interactions of human nuclear proteins P1Mcm3 and P1Cdc46.
1995,
Pubmed
Chang,
Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication.
2015,
Pubmed
Coster,
Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase.
2014,
Pubmed
Deegan,
MCM: one ring to rule them all.
2016,
Pubmed
DePamphilis,
Regulating the licensing of DNA replication origins in metazoa.
2006,
Pubmed
Donovan,
Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast.
1997,
Pubmed
,
Xenbase
Edwards,
MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts.
2002,
Pubmed
,
Xenbase
Frigola,
ATPase-dependent quality control of DNA replication origin licensing.
2013,
Pubmed
Frolova,
Xenopus Cdc6 performs separate functions in initiating DNA replication.
2002,
Pubmed
,
Xenbase
Gambus,
MCM2-7 form double hexamers at licensed origins in Xenopus egg extract.
2011,
Pubmed
,
Xenbase
Gardner,
The High-Affinity Interaction between ORC and DNA that Is Required for Replication Licensing Is Inhibited by 2-Arylquinolin-4-Amines.
2017,
Pubmed
,
Xenbase
Ge,
Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress.
2007,
Pubmed
Gillespie,
Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins.
2001,
Pubmed
,
Xenbase
Harvey,
CpG methylation of DNA restricts prereplication complex assembly in Xenopus egg extracts.
2003,
Pubmed
,
Xenbase
Hyrien,
How MCM loading and spreading specify eukaryotic DNA replication initiation sites.
2016,
Pubmed
Ilves,
Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins.
2010,
Pubmed
Kang,
Multiple functions for Mcm2-7 ATPase motifs during replication initiation.
2014,
Pubmed
Li,
Loading and activation of DNA replicative helicases: the key step of initiation of DNA replication.
2013,
Pubmed
Li,
Structure of the eukaryotic MCM complex at 3.8 Å.
2015,
Pubmed
Mahbubani,
Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor.
1997,
Pubmed
,
Xenbase
Maiorano,
XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
2000,
Pubmed
,
Xenbase
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Ode,
Inter-origin cooperativity of geminin action establishes an all-or-none switch for replication origin licensing.
2011,
Pubmed
,
Xenbase
Oehlmann,
The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.
2004,
Pubmed
,
Xenbase
Powell,
Dynamic loading and redistribution of the Mcm2-7 helicase complex through the cell cycle.
2015,
Pubmed
Remus,
Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.
2009,
Pubmed
Ritzi,
Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin.
1998,
Pubmed
Rowles,
Changes in association of the Xenopus origin recognition complex with chromatin on licensing of replication origins.
1999,
Pubmed
,
Xenbase
Samel,
A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2-7 onto DNA.
2014,
Pubmed
Sanuki,
RecQ4 promotes the conversion of the pre-initiation complex at a site-specific origin for DNA unwinding in Xenopus egg extracts.
2015,
Pubmed
,
Xenbase
Shinya,
Evolutionary diversification of MCM3 genes in Xenopus laevis and Danio rerio.
2014,
Pubmed
,
Xenbase
Sun,
Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA.
2013,
Pubmed
Tanaka,
Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs.
1997,
Pubmed
Tanaka,
Helicase activation and establishment of replication forks at chromosomal origins of replication.
2013,
Pubmed
Tanaka,
Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase.
2002,
Pubmed
Ticau,
Mechanism and timing of Mcm2-7 ring closure during DNA replication origin licensing.
2017,
Pubmed
Ticau,
Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading.
2015,
Pubmed
Waga,
Dynamics of DNA binding of replication initiation proteins during de novo formation of pre-replicative complexes in Xenopus egg extracts.
2006,
Pubmed
,
Xenbase
Woodward,
Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress.
2006,
Pubmed
,
Xenbase
Wühr,
Deep proteomics of the Xenopus laevis egg using an mRNA-derived reference database.
2014,
Pubmed
,
Xenbase
Wyrick,
Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins.
2001,
Pubmed
Yeeles,
Regulated eukaryotic DNA replication origin firing with purified proteins.
2015,
Pubmed
