Abstract
The replicative helicase unwinds parental double-stranded DNA at a replication fork to provide single-stranded DNA templates for the replicative polymerases. In eukaryotes, the replicative helicase is composed of the Cdc45 protein, the heterohexameric ring-shaped Mcm2-7 complex, and the tetrameric GINS complex (CMG). The CMG proteins bind directly to DNA, as demonstrated by experiments with purified proteins. The mechanism and function of these DNA-protein interactions are presently being investigated, and a number of important discoveries relating to how the helicase proteins interact with DNA have been reported recently. While some of the protein-DNA interactions directly relate to the unwinding function of the enzyme complex, other protein-DNA interactions may be important for minichromosome maintenance (MCM) loading, origin melting or replication stress. This review describes our current understanding of how the eukaryotic replicative helicase subunits interact with DNA structures in vitro, and proposed models for the in vivo functions of replicative helicase-DNA interactions are also described.
Highlights
Introduction to DNA Replication andMcm2-7During late M and G1 phases of the cell cycle, the Mcm2-7 complex is loaded as a double-hexamer to encircle double-stranded DNA at an origin (Figure 1)
We found that Cdc45 interaction with single-stranded DNA weakened the interaction between Cdc45 and Mcm2-7, suggesting that Cdc45 interaction with 60-mer single-stranded DNA may stall the replicative helicase [44]
Interaction between Mcm2-7 and single-stranded DNA is required for powered-motion of the helicase along the leading
Summary
During late M and G1 phases of the cell cycle, the Mcm complex is loaded as a double-hexamer to encircle double-stranded DNA at an origin (Figure 1). The Cdc45-Mcm2-7-GINS complex (CMG), fully assembled in S phase, is the replicative helicase in eukaryotes [2]. Mcm is a two-tiered ring comprised of the N-terminal domain (NTD), origin DNA [7,8]. Mcm is a two-tiered ring comprised of the N-terminal domain (NTD), required for required for double hexamer attachment, and a AAA+ C-terminal domain (CTD) that provides the double hexamer attachment, and a(Figure. Mcm2-7hexamer hexameris is domain provides allthe of ATPase activity in the replicative helicase. Complex, the Mcm AAA+ ATPase subunits form a right-handed spiral around ssDNA
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