A structural framework for replication origin opening by AAA+ initiation factors.

ATP-dependent initiation factors help process replication origins and coordinate replisome assembly to control the onset of DNA synthesis. Although the specific properties and regulatory mechanisms of initiator proteins can vary greatly between different organisms, certain nucleotide-binding elements and assembly patterns appear preserved not only within the three domains of cellular life (bacteria, archaea, and eukaryotes), but also with certain classes of double-stranded DNA viruses. Structural studies of replication initiation proteins, both as higher-order oligomers and in complex with cognate DNA substrates, are revealing how an evolutionarily related ATPase fold can support different modes of macromolecular assembly and function. Comparative studies between initiation systems in turn provide clues as to how duplex origin regions may be melted during initiation events.