The eukaryotic Mcm2-7 replicative helicase

Subcell Biochem. 2012:62:113-34. doi: 10.1007/978-94-007-4572-8_7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA / biosynthesis*
  • DNA / genetics
  • Humans
  • Minichromosome Maintenance Proteins / chemistry
  • Minichromosome Maintenance Proteins / genetics
  • Minichromosome Maintenance Proteins / metabolism*
  • Replication Origin / physiology*
  • S Phase / physiology*

Substances

  • CDC45 protein, human
  • Cell Cycle Proteins
  • DNA
  • Minichromosome Maintenance Proteins