The mechanism of eukaryotic CMG helicase activation

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The eukaryotic CMG helicase pumpjack and integration into the replisome

The eukaryotic replisome is α multiprotein machine that contains DNA polymerases, sliding clamps, helicase, and primase along with several factors that participate in cell cycle and checkpoint control. The detailed structure of the 11-subunit CMG helicase (Cdc45/Mcm2-7/GINS) has been solved recently by cryoEM single-particle 3D reconstruction and reveals pumpjack motions that imply an unexpecte...

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Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation

In eukaryotes, two Mcm2–7 rings are loaded onto DNA at origins of replication during G1 phase1,2. The double hexamer is inactive as a heli­ case but is activated upon entry into S phase by the Dbf4­dependent Cdc7 kinase, cyclin­dependent kinase and several transient factors that activate origins; subsequently, Cdc45 and GINS assemble onto each Mcm2–7 complex, thereby forming two active CMG heli...

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DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome

The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPγS and a DNA duplex bearing a 3' single-stranded tail. The structure shows that the MCM subunits of the CMG bind preferentially to single-stra...

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Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase.

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Replicative helicases are ring-shaped hexamers that encircle DNA for duplex unwinding. The currently accepted view of hexameric helicase function is by steric exclusion, where the helicase encircles one DNA strand and excludes the other, acting as a wedge with an external DNA unwinding point during translocation. Accordingly, strand-specific blocks only affect these helicases when placed on the...

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ژورنال

عنوان ژورنال: Nature

سال: 2018

ISSN: 0028-0836,1476-4687

DOI: 10.1038/nature25787