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PMID: 12524516 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A rotary pumping model for helicase function of MCM proteins at a distance from replication forks.

EMBO reports ·Vol. 4 ·No. 1 ·2003-01-00 ·Pages 26-30

Laskey RA, Madine MA

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.

MeSH Terms
Adenosine Triphosphatases/chemistry,physiology Animals DNA Helicases/chemistry,physiology DNA Replication/physiology DNA-Binding Proteins/physiology Energy Metabolism Eukaryotic Cells/cytology,metabolism Female Humans Hydrolysis Macromolecular Substances Male Models, Chemical Molecular Motor Proteins/physiology Motion Nucleic Acid Conformation Prokaryotic Cells/cytology,metabolism Protein Conformation Replication Origin Rotation
Chemicals
DNA-Binding Proteins Macromolecular Substances Molecular Motor Proteins Adenosine Triphosphatases DNA Helicases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Laskey Ronald A
MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK. [email protected]
Madine Mark A
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.embor706
Email
[email protected]
Published
2003-01-00
Pages
26-30
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1315806
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.embor706 PMC Full Text View journal details
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