AAA+ ATPases in the initiation of DNA replication

Karl E. Duderstadt, James M. Berger

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


All cellular organisms and many viruses rely on large, multi-subunit molecular machines, termed replisomes, to ensure that genetic material is accurately duplicated for transmission from one generation to the next. Replisome assembly is facilitated by dedicated initiator proteins, which serve to both recognize replication origins and recruit requisite replisomal components to the DNA in a cell-cycle coordinated manner. Exactly how imitators accomplish this task, and the extent to which initiator mechanisms are conserved among different organisms have remained outstanding issues. Recent structural and biochemical findings have revealed that all cellular initiators, as well as the initiators of certain classes of double-stranded DNA viruses, possess a common adenine nucleotide-binding fold belonging to the ATPases Associated with various cellular Activities (AAA+) family. This review focuses on how the AAA+ domain has been recruited and adapted to control the initiation of DNA replication, and how the use of this ATPase module underlies a common set of initiator assembly states and functions. How biochemical and structural properties correlate with initiator activity, and how species-specific modifications give rise to unique initiator functions, are also discussed.

Original languageEnglish (US)
Pages (from-to)163-187
Number of pages25
JournalCritical reviews in biochemistry and molecular biology
Issue number3
StatePublished - May 2008
Externally publishedYes


  • AAA+ ATPase
  • Clamp loader
  • DNA replication
  • Helicase loader
  • Initiator
  • Superfamily III helicase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


Dive into the research topics of 'AAA+ ATPases in the initiation of DNA replication'. Together they form a unique fingerprint.

Cite this