The DNA polymerase III holoenzyme is the 17-subunit multimeric enzyme responsible for synthesis of bacterial genomic DNA. It is a highly efficient molecular machine, able to coordinate the dynamic cycling of multiple protein components due to a network of interactions that has been finely tuned in strength by nature.  Directly encompassing the nascent DNA strand is a complex of four proteins: the α polymerase subunit, the ε proofreading exonuclease subunit, the small θ subunit and the β₂ sliding clamp. We have used a variety of techniques including crystallography, NMR, single-molecule DNA replication assays, mass spectrometry and SPR to piece together an atomic resolution model of the αεθ-β₂-DNA replicase complex in the polymerisation mode. A particular challenge has been to precisely position the ε subunit in this complex and to understand the conformational changes that occur when the replicase switches into the proofreading mode. The new interactions we have discovered have provided considerable insight into the underlying biochemistry of exonuclease function.