An explanation for lagging strand replication: polymerase hopping among DNA sliding clamps.

The replicase of E. coli, DNA polymerase III holoenzyme, is tightly fastened 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. This study shows that DNA polymerase III holoenzyme cycles from one DNA to another by a novel mechanism of partial disassembly of its multisubunit structure and then reassembly. Upon completing a template, the polymerase disengages from its beta clamp, hops off DNA, and reassociates with another beta clamp at a new primed site. The original beta clamp is left on DNA and may be harnessed by other machineries to coordinate their action with chromosome replication.