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BioEssays
Article . 2018 . Peer-reviewed
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BioEssays
Article . 2019
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The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

Authors: Huilin, Li; Michael E, O'Donnell;

The Eukaryotic CMG Helicase at the Replication Fork: Emerging Architecture Reveals an Unexpected Mechanism

Abstract

The eukaryotic helicase is an 11‐subunit machine containing an Mcm2‐7 motor ring that encircles DNA, Cdc45 and the GINS tetramer, referred to as CMG (Cdc45, Mcm2‐7, GINS). CMG is “built” on DNA at origins in two steps. First, two Mcm2‐7 rings are assembled around duplex DNA at origins in G1 phase, forming the Mcm2‐7 “double hexamer.” In a second step, in S phase Cdc45 and GINS are assembled onto each Mcm2‐7 ring, hence producing two CMGs that ultimately form two replication forks that travel in opposite directions. Here, we review recent findings about CMG structure and function. The CMG unwinds the parental duplex and is also the organizing center of the replisome: it binds DNA polymerases and other factors. EM studies reveal a 20‐subunit core replisome with the leading Pol ϵ and lagging Pol α‐primase on opposite faces of CMG, forming a fundamentally asymmetric architecture. Structural studies of CMG at a replication fork reveal unexpected details of how CMG engages the DNA fork. The structures of CMG and the Mcm2‐7 double hexamer on DNA suggest a completely unanticipated process for formation of bidirectional replication forks at origins.

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Keywords

DNA Replication, Models, Molecular, Binding Sites, Saccharomyces cerevisiae Proteins, Minichromosome Maintenance Proteins, G1 Phase, Nuclear Proteins, DNA, Saccharomyces cerevisiae, Protein Structure, Secondary, DNA-Binding Proteins, Xenopus laevis, Drosophila melanogaster, Animals, Humans, Nucleic Acid Conformation, Protein Multimerization, Encephalitozoon cuniculi, Protein Binding

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    70
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
70
Top 10%
Top 10%
Top 1%
bronze