The Eukaryotic Mcm2-7 Replicative Helicase

Part of the Subcellular Biochemistry book series (SCBI, volume 62)

Abstract

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.

Keywords

Mcm2-7 DNA replication Gate model AAA+ proteins GINS Cdc45 Cell cycle 

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of PittsburghPittsburghUSA

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