Novel role of DONSON in CMG helicase assembly during vertebrate DNA replication initiation [PDF]
EMBO Journal, 2023 Yoshitami Hashimoto
exaly +2 more sources
CMG helicase activity on G4-containing DNA templates. [PDF]
Methods Enzymol, 2022 G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in G-rich regions of the genome and threaten genome stability by interfering with DNA replication. However, the underlying mechanisms are poorly understood. We have recently found that G4s can stall eukaryotic replication forks by blocking the progression of replicative DNA ...
Batra S, Devbhandari S, Remus D.
europepmc +3 more sources
The CMG helicase and cancer: a tumor "engine" and weakness with missing mutations. [PDF]
Oncogene, 2023 The replicative Cdc45-MCM-GINS (CMG) helicase is a large protein complex that functions in the DNA melting and unwinding steps as a component of replisomes during DNA replication in mammalian cells. Although the CMG performs this important role in cell growth, the CMG is not a simple bystander in cell cycle events.
Xiang S, Reed DR, Alexandrow MG.
europepmc +3 more sources
Myc and the Replicative CMG Helicase: The Creation and Destruction of Cancer: Myc Over-Activation of CMG Helicases Drives Tumorigenesis and Creates a Vulnerability in CMGs for Therapeutic Intervention. [PDF]
Bioessays, 2020 AbstractMyc‐driven tumorigenesis involves a non‐transcriptional role for Myc in over‐activating replicative Cdc45‐MCM‐GINS (CMG) helicases. Excessive stimulation of CMG helicases by Myc mismanages CMG function by diminishing the number of reserve CMGs necessary for fidelity of DNA replication and recovery from replicative stresses.
Reed DR, Alexandrow MG.
europepmc +5 more sources
CMG helicase can use ATPγS to unwind DNA: Implications for the rate-limiting step in the reaction mechanism [PDF]
Proceedings of the National Academy of Sciences of the United States of America, 2022 Michael O'Donnell +2 more
exaly +2 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,
Liu W +6 more
europepmc +3 more sources
DNA translocation by the CMG helicase: the helical inchworm model. [PDF]
Biochem Soc TransAbstract In all cells, hexameric helicases drive the unwinding of parental chromosomal DNA at replication forks to provide the single-stranded DNA templates required by replicative DNA polymerases. DNA unwinding proceeds via a steric exclusion mechanism in which the helicase encircles and translocates along one DNA strand while ...
Batra S +4 more
europepmc +3 more sources
Mechanisms of MCM2–7 helicase activation and initial DNA melting at near base-pair resolution [PDF]
Nature CommunicationsDuring eukaryotic DNA replication initiation, inactive MCM2–7 double-hexamers assembled at replication origins must be converted into two active CMG helicases, yet how this transition is coupled to origin DNA unwinding in vivo remains unclear.
Christopher Weekes +11 more
doaj +2 more sources
Cellular replisomes are powered by flex-fuel motors for unwinding DNA [PDF]
Nature CommunicationsDNA replication relies on hexameric, ring-shaped helicases to unwind parental DNA for supporting fork progression over tens of thousands of base pairs. Oddly, biochemical studies have suggested that, on their own, replicative helicases are rather limited
Fahad Rashid +7 more
doaj +2 more sources
Identification of ATP-Competitive Human CMG Helicase Inhibitors for Cancer Intervention that Disrupt CMG-Replisome Function. [PDF]
Mol Cancer TherAbstract 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