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Updated: Jul 20, 2026

Hybrid Ensemble and Single-molecule Assay to Image the Motion of Fully Reconstituted CMG
Published on: July 26, 2024
Cdc45-MCM-GINS, a new power player for DNA replication
Tomás Aparicio1, Arkaitz Ibarra, Juan Méndez
1DNA replication Group, Molecular Oncology Programme, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro 3, E-28029 Madrid, Spain. taparicio@cnio.es
Abstract:
The identity of the DNA helicase(s) involved in eukaryotic DNA replication is still a matter of debate, but the mini-chromosome maintenance (MCM) proteins are the chief candidate. Six conserved MCM proteins, Mcm2-7, are essential for the initiation and elongation stages of DNA replication, contain ATP binding pockets and can form a hexameric structure resembling that of known prokaryotic and viral helicases. However, biochemical proof of their presumed function has remained elusive. Several recent reports confirm that the MCM complex is part of the cellular machine responsible for the unwinding of DNA during S phase. In one of these reports, the helicase activity of Mcm2-7 is finally revealed, when they are purified in association with two partners: initiation factor Cdc45 and a four-subunit complex called GINS. The Cdc45-MCM-GINS complex could constitute the core of a larger macromolecular structure that has been termed the "replisome progression complex".
Insights
The mini-chromosome maintenance (MCM) complex, essential for DNA replication, has demonstrated helicase activity. This discovery confirms MCM proteins
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- The precise DNA helicase responsible for eukaryotic DNA replication remains unidentified.
- Mini-chromosome maintenance (MCM) proteins (Mcm2-7) are key candidates due to their structural and functional characteristics.
- Biochemical evidence for MCM helicase activity has been lacking.
Purpose of the Study:
- To provide biochemical evidence for the helicase activity of the MCM complex.
- To identify the protein partners associated with MCM during DNA replication.
- To elucidate the composition of the core replication machinery.
Main Methods:
- Purification of MCM proteins in association with other factors.
- Biochemical assays to detect helicase activity.
- Characterization of the purified complex.
Main Results:
- The MCM complex (Mcm2-7) was purified with initiation factor Cdc45 and the GINS complex.
- The purified Cdc45-MCM-GINS complex exhibited DNA helicase activity.
- This complex is proposed to be a core component of the replisome progression complex.
Conclusions:
- The MCM complex, in conjunction with Cdc45 and GINS, functions as the eukaryotic DNA helicase.
- This finding clarifies the molecular mechanism of DNA replication initiation and elongation.
- The Cdc45-MCM-GINS complex represents a fundamental unit of the replication machinery.
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