The architecture of the E. coli replisome at a replication fork. DnaB helicase encircles the lagging strand, and the Pol III holoenzyme connects to DnaB via the τ subunits of the clamp loader. The holoenzyme contains three Pol III cores. In the illustration, two Pol III cores connect to β clamps on the leading and lagging strands. The function of the third Pol III is discussed in the text. Primase (DnaG) transiently associates with DnaB for the synthesis of an RNA primer on the lagging strand. The lagging-strand Pol III core–β clamp travels with the replisome, yet extends DNA in the 5′→3′ direction, resulting in a DNA loop. The lagging strand is bound by SSB. The clamp loader is shown bound to a β clamp that it has opened in preparation for loading the clamp onto the RNA primer.