Eukaryotic DNA replication control: lock and load, then fire

Curr Opin Cell Biol. 2009 Dec;21(6):771-7. doi: 10.1016/ Epub 2009 Sep 18.


The initiation of chromosomal DNA replication involves initiator proteins that recruit and load hexameric DNA helicases at replication origins. This helicase loading step is tightly regulated in bacteria and eukaryotes. In contrast to the situation in bacteria, the eukaryotic helicase is loaded in an inactive form. This extra 'lock and load' mechanism in eukaryotes allows regulation of a second step, helicase activation. The temporal separation of helicase loading and activation is crucial for the coordination of DNA replication with cell growth and extracellular signals, the prevention of re-replication and the control of origin activity in response to replication stress. Initiator proteins in bacteria and eukaryotes are structurally homologous; yet the replicative helicases they load are unrelated. Understanding how these helicases are loaded and how they act during unwinding may have important implications for understanding how DNA replication is regulated in different domains of life.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Replication*
  • DnaB Helicases / genetics
  • DnaB Helicases / metabolism
  • Eukaryota / genetics*
  • Eukaryota / physiology
  • Humans
  • Models, Biological
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism


  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA
  • dnaB protein, E coli
  • DNA Helicases
  • DnaB Helicases