A rotary pumping model for helicase function of MCM proteins at a distance from replication forks.
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.
Laskey
Ronald A
RA
MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 2XZ, UK. ral@hutchison-mrc.cam.ac.uk
Madine
Mark A
MA
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000502:physiology; D000818:Animals; D004265:DNA Helicases / Q000737:chemistry / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004734:Energy Metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D046911:Macromolecular Substances; D008297:Male; D008956:Models, Chemical; D020409:Molecular Motor Proteins / Q000502:physiology*; D009038:Motion; D009690:Nucleic Acid Conformation; D011387:Prokaryotic Cells / Q000166:cytology / Q000378:metabolism; D011487:Protein Conformation; D018741:Replication Origin; D012399:Rotation
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D020409:Molecular Motor Proteins; D000251:Adenosine Triphosphatases; D004265:DNA Helicases