The replicase of E. coli, DNA polymerase III holoenzyme, is tightly fa
stened to DNA by its ring-shaped beta sliding clamp. However, despite
being clamped to DNA, the polymerase must rapidly cycle on and off DNA
to synthesize thousands of Okazaki fragments on the lagging strand. T
his study shows that DNA polymerase III holoenzyme cycles from one DNA
to another by a novel mechanism of partial disassembly of its multisu
bunit structure and then reassembly. Upon completing a template, the p
olymerase disengages from its beta clamp, hops off DNA, and reassociat
es with another beta clamp at a new primed site. The original beta cla
mp is left on DNA and may be harnessed by other machineries to coordin
ate their action with chromosome replication.