The eukaryotic CMG helicase pumpjack and integration into the replisome

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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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Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase

Replisome assembly at eukaryotic replication forks connects the DNA helicase to DNA polymerases and many other factors. The helicase binds the leading-strand polymerase directly, but is connected to the Pol α lagging-strand polymerase by the trimeric adaptor Ctf4. Here, we identify new Ctf4 partners in addition to Pol α and helicase, all of which contain a "Ctf4-interacting-peptide" or CIP-box....

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Tethering of SCFDia2 to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase

Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood. In budding yeast, the F-box protein Dia2 drives ubiquitylation of the CMG helicase at the end of replication, leading to a disassembly pathway that requires the Cdc48 segregase. The substra...

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ژورنال

عنوان ژورنال: Nucleus

سال: 2016

ISSN: 1949-1034,1949-1042

DOI: 10.1080/19491034.2016.1174800