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A rotary pumping model for helicase function of MCM proteins at a distance from replication forks
Author(s) -
Laskey Ronald A,
Madine Mark A
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor706
Subject(s) - helicase , control of chromosome duplication , dna replication , minichromosome maintenance , eukaryotic dna replication , microbiology and biotechnology , origin recognition complex , biology , dna , fork (system call) , prokaryotic dna replication , dnab helicase , circular bacterial chromosome , genetics , biophysics , computer science , gene , rna , operating system
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.