Two replication initiators – one mechanism for replication origin opening?

• Quaternary structure of Rep protein affects its stability and accessibility.
• The crystallographic data on Rep protein structures is mainly limited to WH domains.
• DnaA is structurally different from plasmid Rep proteins.
• Both DnaA and plasmid Rep protein interact with ssDNA of the DUE region.
• The structure of protein–DNA complexes within DUE is still ambiguous.

DNA replication initiation has been well-characterized; however, studies in the past few years have shown that there are still important discoveries to be made. Recent publications concerning the bacterial DnaA protein have revealed how this replication initiator, via interaction with specific sequences within the origin region, causes local destabilization of double stranded DNA. Observations made in the context of this bacterial initiator have also been converging with those recently made for plasmid Rep proteins. In this mini review we discuss the relevance of new findings for the RK2 plasmid replication initiator, TrfA, with regard to new data on the structure of complexes formed by the chromosomal replication initiator DnaA. We discuss structure–function relationships of replication initiation proteins.