DNA polymerase III holoenzyme is the principal replicative enzyme of E. coli. High catalytic rates are achieved by having the polymerase subunit (called alpha) of the 10- subunit enzyme clamped to the template by auxiliary subunits; its high fidelity of replication is achieved by complexing of the alpha subunit with the epsilon subunit to enable effective proofreading at the growing end of the chain. The holoenzyme is in fact part of a more complex machine which contains two polymerase subunits and together with priming proteins and helicases may constitute a "replisome." Seated at the replication fork of a chromosome, the replisome may effect a relatively concurrent replication of both strands of the duplex chromosome rather than the spasmodic, jerky, semidiscontinuous model now in use. Toward establishing the detailed structure and individual functions of several forms of this extraordinary polymerase molecule, various techniques of genetic engineering, protein isolation, immunocyto- chemistry, electron microscopy and enzymology will be used. The significance of understanding replication in molecular detail lies in its application toward the development of drugs to interrupt the process in proliferative diseases, such as cancer, and the acquisition of new insights into growth processes and their aberrations.
