The replication clamp-loading machine at work in the three domains of life

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Abstract
Processive DNA polymerases that replicate chromosomes interact with a ring-shaped clamp that encircles DNA and slides along the duplex. All sliding clamps (Escherichia coli β-clamp, T4 bacteriophage gp45, archaeal and eukaryotic proliferating cell nuclear antigen (PCNA)) form similar planar ring structures with a central channel of sufficient width to encircle duplex DNA. In all the clamps, the two faces of the ring are structurally distinct and polymerases and clamp loaders compete for binding to the same face. Therefore, the clamp loader must depart from the clamp for the DNA polymerase to function. The sliding clamp is loaded onto DNA by a clamp-loader complex driven by ATP. Clamp loaders are circular heteropentameric complexes that have been conserved throughout evolution and their subunits are members of the AAA+ (ATPases associated with a variety of cellular activities) family of ATPases. The ATP-binding sites of clamp loaders are located at subunit interfaces. Although clamp loaders are very similar in structure and function, the specifics of ATP use varies among different replication systems. Insights into the way clamp loaders bind to DNA, recognize a primer–template junction, and open the clamp have been revealed by recent structural and biochemical studies. The findings of these studies indicate that the clamp assumes a right-handed spiral configuration when it opens, and it docks onto the helical surface of the clamp loader.