The eukaryotic Mcm2-7 replicative helicase.
In eukaryotes, the Mcm2-7 complex forms the core of the replicative helicase - the molecular motor that uses ATP binding and hydrolysis to fuel the unwinding of double-stranded DNA at the replication fork. Although it is a toroidal hexameric helicase superficially resembling better-studied homohexameric helicases from prokaryotes and viruses, Mcm2-7 is the only known helicase formed from six unique and essential subunits. Recent biochemical and structural analyses of both Mcm2-7 and a higher-order complex containing additional activator proteins (the CMG complex) shed light on the reason behind this unique subunit assembly: whereas only a limited number of specific ATPase active sites are needed for DNA unwinding, one particular ATPase active site has evolved to form a reversible discontinuity (gate) in the toroidal complex. The activation of Mcm2-7 helicase during S-phase requires physical association of the accessory proteins Cdc45 and GINS; structural data suggest that these accessory factors activate DNA unwinding through closure of the Mcm2-7 gate. Moreover, studies capitalizing on advances in the biochemical reconstitution of eukaryotic DNA replication demonstrate that Mcm2-7 loads onto origins during initiation as a double hexamer, yet does not act as a double-stranded DNA pump during elongation.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Sriram
S
Vijayraghavan
Anthony
A
Schwacha
D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018741:Replication Origin / Q000502:physiology*; D016196:S Phase / Q000502:physiology*
C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D004247:DNA; D064110:Minichromosome Maintenance Proteins