The mechanism of eukaryotic CMG helicase activation. [PDF]
The initiation of eukaryotic DNA replication occurs in two discrete stages: first, the minichromosome maintenance (MCM) complex assembles as a head-to-head double hexamer that encircles duplex replication origin DNA during G1 phase; then, 'firing factors' convert each double hexamer into two active Cdc45-MCM-GINS helicases (CMG) during S phase.
Douglas ME +3 more
europepmc +4 more sources
Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function. [PDF]
Abstract The human CMG helicase (Cdc45-MCM-GINS) is a novel target for anticancer therapy. Tumor-specific weaknesses in the CMG are caused by oncogene-driven changes that adversely affect CMG function, and CMG activity is required for recovery from replicative stresses such as chemotherapy.
Xiang S +8 more
europepmc +3 more sources
The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo [PDF]
We report that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for differential gene expression in cells produced by asymmetric cell divisions in C. elegans. We found that the C.
Nadin Memar +8 more
doaj +3 more sources
The eukaryotic CMG helicase pumpjack and integration into the replisome. [PDF]
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 ...
Sun J +4 more
europepmc +4 more sources
MCM7 Ubiquitination Regulates CMG Helicase Disassembly In Human [PDF]
Abstract The disassembly of the replisome plays an essential role in maintaining genome stability at the termination of DNA replication. However, the mechanism of replisome disassembly remains unknown in human. In this study, we screened E3 ligases and deubiquitinases (DUBs) for the ubiquitination of minichromosome maintenance protein (MCM) 7 ...
Qianqian Sun +7 more
openaire +2 more sources
Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation [PDF]
Roxana E Georgescu +2 more
exaly +2 more sources
In eukaryotes, the perfect duplication of the chromosomes is executed by a dynamic molecular machine called the replisome. As a key step to finishing DNA replication, replisome disassembly is triggered by ubiquitylation of the MCM7 subunit of the ...
Yisui Xia
doaj +1 more source
The CMG DNA helicase and the core replisome
Eukaryotic DNA replication is performed by the replisome, a large and dynamic multi-protein machine endowed with the required enzymatic components for the synthesis of new DNA. Recent cryo-electron microscopy (cryoEM) analyses have revealed the conserved architecture of the core eukaryotic replisome, comprising the CMG (Cdc45-MCM-GINS) DNA helicase ...
openaire +2 more sources
Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest. [PDF]
Significance Programmed replication fork arrest (PFA) at specific terminator sites and the proteins that bind to these sites functionally interconnect replication, transcription, and recombination. PFA prevents collision between replication and transcription that can cause genome instability, promotes intrachromatid recombination at ribosomal
Bastia D +8 more
europepmc +4 more sources
Rad53 limits CMG helicase uncoupling from DNA synthesis at replication forks. [PDF]
The coordination of DNA unwinding and synthesis at replication forks promotes efficient and faithful replication of chromosomal DNA. Disruption of the balance between helicase and polymerase activities during replication stress leads to fork progression defects and activation of the Rad53 checkpoint kinase, which is essential for the functional ...
Devbhandari S, Remus D.
europepmc +4 more sources

