Structural dynamics and protein interactions within the E. coli DNA polymerase III holoenzyme

DNA replication is an essential process that must proceed from start to end without failure. The Escherichia coli cellular replication machine or “replisome” is composed of a dozen or so different proteins. At the heart of the replisome is the DNA polymerase III holoenzyme (Pol III HE). We have established a detailed picture of the enzymatic abilities and functions of the Pol III HE, and as a result uncovered many of the protein– protein interactions essential for its function. How many of these protein–protein interactions allow the replisome to transition from one conformational state to another remains either speculative or unknown. The main aims of this project were to study the interactions that allow for a dynamic replisome, to better understand the hierarchy of strong and weak functional interactions within the Pol III HE.