The ring-type polymerase sliding clamp family

Abstract

Ring-type polymerases consist of a DNA polymerase, a ring-shaped sliding clamp protein and a clamp-loading complex. Sliding clamp proteins are found in all organisms and are called proliferating cell nuclear antigen (PCNA) in eukaryotes and the beta clamp in prokaryotes. Both PCNA and beta form a ring around DNA, which is made up of two subunits of three domains each in beta but three subunits of two domains each in PCNA. Despite this difference and a lack of detectable sequence homology, the structures of the two rings are very similar. The sliding clamp slides along DNA and tethers the polymerase to the DNA, enabling rapid and processive DNA replication.

Figure 1

Sliding clamp rings of different organisms. Clamps are constructed from either two or three monomers to yield a ring composed of six domains. (a) The prokaryotic β subunit contains three domains, whereas PCNA and T4 gp45 are about two thirds the size of β and comprise only two domains each. The crystal structures of the oligomeric rings: (b)E. coli β; (c) human PCNA; (d) T4 phage gp45. In (b-d), the interfaces between protomers are indicated by the arrows, and the domains within each monomer unit are numbered (1-3 for β and 1,2 for PCNA and gp45).

Figure 2

The action of the three components of the ring-type DNA polymerases. The protein ring (sliding clamp) is assembled onto a primed template junction by a clamp-loader complex in an ATP-driven reaction. The DNA polymerase (Pol) then assembles with the ring on DNA to form a highly processive polymerase, which pulls the ring along behind it during chain extension while remaining tethered to DNA by the ring.