From structure to mechanism-understanding initiation of DNA replication

Genes Dev. 2017 Jun 1;31(11):1073-1088. doi: 10.1101/gad.298232.117.


DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2-7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability.

Keywords: CMG; DNA replication; MCM2–7; cryo-EM; pre-RC; replisome.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / metabolism
  • DNA Helicases / metabolism
  • DNA Replication / genetics
  • DNA Replication / physiology*
  • Evolution, Molecular
  • Genomic Instability / genetics
  • Humans
  • Minichromosome Maintenance Proteins / genetics
  • Minichromosome Maintenance Proteins / metabolism
  • Replication Origin / physiology


  • Chromatin
  • DNA Helicases
  • Minichromosome Maintenance Proteins