A new model for copy numb er control of the plasmid R1 has been develo
p ed. It takes into account that initiation of replication of R1 requi
res a large number of cis-acting proteins (RepA). The theory explains
how plasmid production rates respond to shifts in external conditions.
It predicts the observed ''eclipse'' times between two plasmid duplic
ations as well as the replication time for ''runaway'' plasmids lackin
g the antisense inhibitor CopA. The model also describes how the use o
f many cis-acting RepAs can lead to a tight coupling between cell and
plasmid cycles that minimizes the rate of the plasmid loss. The result
s may be used as a guideline for construction of low copy number plasm
ids with high maintenance stability.