A rotary pumping model for helicase function of MCM proteins at a distance from replication forks
Related Experiment Video
Updated: Sep 27, 2026

Hybrid Ensemble and Single-molecule Assay to Image the Motion of Fully Reconstituted CMG
Published on: July 26, 2024
Ronald A Laskey1, Mark A Madine
1MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK. ral@hutchison-mrc.cam.ac.uk
Abstract:
We propose an integrated model for eukaryotic DNA replication to explain the following problems: (1) How is DNA spooled through fixed sites of replication? (2) What and where are the helicases that unwind replicating DNA? (3) Why are the best candidates for replicative helicases, namely mini-chromosome maintenance (MCM) proteins, not concentrated at the replication fork? (4) How do MCM proteins spread away from loading sites at origins of replication? We draw on recent discoveries to argue that the MCM hexameric ring is a rotary motor that pumps DNA along its helical axis by simple rotation, such that the movement resembles that of a threaded bolt through a nut, and we propose that MCM proteins act at a distance from the replication fork to unwind DNA. This model would place DNA replication in a growing list of processes, such as recombination and virus packaging, that are mediated by ring-shaped ATPases pumping DNA by helical rotation.
Related Concept Videos
Restarting Stalled Replication Forks
Restarting Stalled Replication Forks
DNA Helicases
The Replisome
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
Homologous Recombination
The DNA Replication Fork

