The replication of the DNA of Escherichia coli proceeds via the replisome, a multiprotein workhorse that in other organisms may vary in complexity. The replisome is made up of two DNA polymerase III core enzymes (DNA pol III), which are each made up of three subunits: one with polymerization activity, one with proofreading ability and one that stimulates the proofreading. Mutations in these subunits are often lethal, as replication is an essential function that a cell must carry out before division. Each protein in the replisome has a subunit or functional name - such as helicase and θ - as well as a name according to the name of its gene - such as dnaB and dnaQ. The goal of these subunits or proteins is to replicate the organism's genome accurately and quickly.
More specifically, in E. coli, the replisome can be thought of as an assembly of the following: two core replicating units with polymerase activity, two ββ clamp units that improve the core's polymerase activity or processivity, a γ/τ clamp loader that attaches the ββ clamps via ATP hydrolysis, units that serve to unwind DNA called helicases, single-stranded binding proteins that protect single-stranded DNA, and a DNA primase that writes the primers necessary for DNA synthesis to begin. The polymerase core consists of the α subunit (DnaE) with polymerase activity, the ε subunit (DnaQ) associated with 3'->5' exonuclease activity, and the θ (HolE) subunit that functions with the ε unit to improve exonuclease activity. The activity of ε is that of proofreading, correcting mismatched base pairs when the α subunit makes mistakes and greatly improving the fidelity of replication. Two β units (DnaN) dimerize to form ββ clamps, which are present in a 10-fold higher concentration (>300 units) than the core polymerase (10-20 units). The ββ clamp resembles a donut or ring and must be opened to load it around DNA at the primer-template site where replication is to take place. The γ/τ clamp loader--which is a collection of three γ/τ proteins (DnaX), one δ (HolA), one δ' (HolB), one χ (HolC), and one ψ (HolD)--opens ββ clamps via δ-β interaction facilitated by ATP binding to γ proteins of the clamp loader. Together, the ββ clamps and γ/τ clamp loader help to improve the processivity or speed of replication. The strands of DNA are unwound by helicases (DnaB), ATP hydrolyzing proteins that must break the hydrogen bonds between the base pairs of DNA. After the DNA has been unwound, the single strands are protected from degradation and the formation of secondary structures by single-stranded binding proteins (SSBP). These SSBPs bind cooperatively to keep the single stranded DNA in a linear conformation, which is essential for the lagging strand, which often has stretches of ssDNA between Okazaki fragments. Finally, a DNA primase (DnaG) is also necessary to make the RNA primers that allow the core enzyme to begin replication activity. On the leading strand, the primase need only act once; however, the lagging strand needs one primer for each Okazaki fragment. Furthermore, for each Okazaki fragment the lagging strand needs a ββ clamp, which must also be loaded by the clamp loader. This requires E. coli to have many more clamps and clamp loaders than core polymerase units. During the synthesis of one Okazaki fragment, the DnaG primase synthesizes the next Okazaki primer, and the clamp loader complex loads the next ββ clamp so that replication may continue without any decrease in processivity.
In eukaryotes, the replisome is similar. In human cells, there exists a helicase (T antigen), loading helicase/primase (T antigen), single strand binding proteins (RPA), primases (Pol α/ primase), sliding clamps (PCNA), clamp loader (RFC), catalyzing unit (Polα), and other units.