title: Activation of the replicative DNA helicase: breaking up is hard to do.
abstract: The precise duplication of the eukaryotic genome is accomplished by carefully coordinating the loading and activation of the replicative DNA helicase so that each replication origin is unwound and assembles functional bi-directional replisomes just once in each cell cycle. The essential Minichromosome Maintenance 2-7 (Mcm2-7) proteins, comprising the core of the replicative DNA helicase, are first loaded at replication origins in an inactive form. The helicase is then activated by recruitment of the Cdc45 and GINS proteins into a holo-helicase known as CMG (Cdc45, Mcm2-7, GINS). These steps are regulated by multiple mechanisms to ensure that Mcm2-7 loading can only occur during G1 phase, whilst activation of Mcm2-7 cannot occur during G1 phase. Here we review recent progress in understanding these critical reactions focusing on the mechanism of helicase loading and activation.
authors.affiliation: Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
authors.forename: Dominik
authors.initials: D
authors.lastname: Boos
authors.forename: Jordi
authors.initials: J
authors.lastname: Frigola
authors.forename: John F X
authors.initials: JF
authors.lastname: Diffley
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication; D004789:Enzyme Activation; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2