The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy [PDF]
Frontiers in Molecular Biosciences, 2018 DNA helicases unwind or rearrange duplex DNA during replication, recombination and repair. Helicases of many pathogenic organisms such as viruses, bacteria, and protozoa have been studied as potential therapeutic targets to treat infectious diseases, and
Yeon-Soo Seo, Young-Hoon Kang
exaly +8 more sources
Structure of human Cdc45 and implications for CMG helicase function [PDF]
Nature Communications, 2016 The cell cycle division protein Cdc45 is required for genome duplication in eukaryotes. Here, the authors determine the crystal structure of human Cdc45 and combine it with functional data to improve our understanding of its role in DNA replication.
Aline C. Simon +3 more
doaj +7 more sources
The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair [PDF]
Cell, 2019 Covalent DNA-protein cross-links (DPCs) impede replication fork progression and threaten genome integrity. Using Xenopus egg extracts, we previously showed that replication fork collision with DPCs causes their proteolysis, followed by translesion DNA synthesis. We show here that when DPC proteolysis is blocked, the replicative DNA helicase CMG (CDC45,
Gheorghe Chistol +2 more
exaly +10 more sources
DONSON is required for CMG helicase assembly in the mammalian cell cycle [PDF]
EMBO Reports, 2023 Abstract DONSON is one of 13 genes mutated in a form of primordial microcephalic dwarfism known as Meier-Gorlin Syndrome. The other 12 encode components of the CDC45-MCM-GINS helicase, around which the eukaryotic replisome forms, or are factors required for helicase assembly during DNA replication initiation.
Cecile Evrin +2 more
exaly +6 more sources
Mechanism of replication origin melting nucleated by CMG helicase assembly. [PDF]
Nature, 2022 AbstractThe activation of eukaryotic origins of replication occurs in temporally separated steps to ensure that chromosomes are copied only once per cell cycle. First, the MCM helicase is loaded onto duplex DNA as an inactive double hexamer. Activation occurs after the recruitment of a set of firing factors that assemble two Cdc45–MCM–GINS (CMG) holo ...
Lewis JS +7 more
europepmc +4 more sources
Reconstitution of human CMG helicase ubiquitylation by CUL2LRR1 and multiple E2 enzymes. [PDF]
Biochem J, 2021 Cullin ubiquitin ligases drive replisome disassembly during DNA replication termination. In worm, frog and mouse cells, CUL2LRR1 is required to ubiquitylate the MCM7 subunit of the CMG helicase. Here, we show that cullin ligases also drive CMG-MCM7 ubiquitylation in human cells, thereby making the helicase into a substrate for the p97 unfoldase.
Le TT +4 more
europepmc +7 more sources
RAD51 bypasses the CMG helicase to promote replication fork reversal [PDF]
Science, 2023 Replication fork reversal safeguards genome integrity as a replication stress response. DNA translocases and the RAD51 recombinase catalyze reversal. However, it remains unknown why RAD51 is required and what happens to the replication machinery during reversal. We find that RAD51 uses its strand exchange activity to circumvent the replicative helicase,
Wenpeng Liu +2 more
exaly +4 more sources
The replicative CMG helicase: the ideal target for cancer therapy [PDF]
The Ukrainian Biochemical Journal, 2020 This review focuses on Cdc45-Mcm2-7-GINS (CMG) helicase which is a key component of the cellular replication machinery and a new promising target for cancer therapy.
W. Henderson +3 more
doaj +2 more sources
Replication Fork Activation Is Enabled by a Single-Stranded DNA Gate in CMG Helicase [PDF]
Cell, 2019 The eukaryotic replicative helicase CMG is a closed ring around double-stranded (ds)DNA at origins yet must transition to single-stranded (ss)DNA for helicase action. CMG must also handle repair intermediates, such as reversed forks that lack ssDNA. Here, using correlative single-molecule fluorescence and force microscopy, we show that CMG harbors a ...
Michael R Wasserman +2 more
exaly +6 more sources
CUL2<sup>LRR1</sup> , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle. [PDF]
EMBO Rep, 2021 Abstract The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of Saccharomyces cerevisiae , Caenorhabditis elegans and Xenopus laevis
Villa F +6 more
europepmc +7 more sources