Eukaryotic DNA replication control: lock and load, then fire

D Remus, JFX Diffley - Current opinion in cell biology, 2009 - Elsevier
Current opinion in cell biology, 2009Elsevier
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 …
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.
Elsevier