Plasmid R6K replication control

► A survey of investigations into the replication control of plasmid R6K is presented. ► Special emphasis is placed on the functional diversity of π/π and π/DNA interactions. ► A simple homeostatic model is offered to account for the regulated usage of R6K’s three replication origins. ► Prospects for the use of the plasmid in antibiotic discovery research are described. The focus of this minireview is the replication control of the 39.9-kb plasmid R6K and its derivatives. Historically, this plasmid was thought to have a narrow host range but more recent findings indicate that its derivatives can replicate in a variety of enteric and non-enteric bacterial species (Wild et al., 2004). In the four-plus decades since it was first described, R6K has proven to be an excellent model for studies of plasmid DNA replication. In part this is because of its similarities to other systems in which replication is activated and regulated by Rep protein and iteron-containing DNA. However its apparent idiosynchracies have also added to its significance (e.g., independent and co-dependent replication origins, and Rep dimers that stably bind iterons). Here, we survey the current state of knowledge regarding R6K replication and place individual regulatory elements into a proposed homeostatic model with implications for the biological significance of R6K and its multiple origins of replication.