Mechanisms and regulation of DNA replication initiation in eukaryotes

Matthew W. Parker, Michael R. Botchan, James M. Berger

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations

Abstract

Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a typical cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the origin recognition complex (ORC), and subsequent activation of the helicase by its incorporation into a complex known as the CMG. Recent work has begun to reveal the details of an orchestrated and sequential exchange of initiation factors on DNA that give rise to a replication-competent complex, the replisome. Here, we review the molecular mechanisms that underpin eukaryotic DNA replication initiation–from selecting replication start sites to replicative helicase loading and activation–and describe how these events are often distinctly regulated across different eukaryotic model organisms.

Original languageEnglish (US)
Pages (from-to)107-144
Number of pages38
JournalCritical reviews in biochemistry and molecular biology
Volume52
Issue number2
DOIs
StatePublished - Mar 4 2017
Externally publishedYes

Keywords

  • CMG
  • Cdc6
  • Cdt1
  • DNA replication
  • MCM2-7
  • ORC
  • helicase
  • initiator

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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