A DNA clamp, also known as a sliding clamp, is a protein fold that serves as a processivity-promoting factor in DNA replication. As a critical component of the DNA polymerase III holoenzyme, the clamp protein binds DNA polymerase and prevents the enzyme from dissociating from the template DNA strand. Because the rate-limiting step in the DNA synthesis reaction is the association of the polymerase with the DNA template, the presence of the sliding clamp dramatically increases the number of nucleotides that the polymerase can add to the growing strand per association event because the clamp-polymerase protein-protein interactions are stronger and more specific than the direct interactions between the polymerase and the template DNA strand. The DNA clamp protein's presence can increase the rate of DNA synthesis up to 1,000-fold versus a nonprocessive polymerase.
The DNA clamp fold is an α+β protein that assembles into a multimeric structure that completely encircles the DNA double helix as the polymerase adds nucleotides to the growing strand. The DNA clamp assembles on the DNA at the replication fork and "slides" along the DNA with the advancing polymerase, aided by a layer of water molecules in the central pore of the toroid-shaped clamp between the DNA and the protein surface. The DNA clamp fold is found in both prokaryotes and eukaryotes and has a rough twofold internal symmetry. Because of the toroidal shape of the assembled multimer, the clamp cannot dissociate from the template strand without also dissociating into monomers.
Sliding clamps are loaded onto their associated DNA template strands by specialized proteins known as "sliding clamp loaders", which also disassemble the clamps after replication has completed. The binding sites for these initiator proteins overlap with the binding sites for the DNA polymerase, so the clamp cannot simultaneously associate with a clamp loader and with a polymerase. Thus the clamp will not be actively disassembled while the polymerase remains bound. Although DNA clamps play a less significant role in associating with other DNA-interacting proteins, such as nucleosome assembly factors, Okazaki fragment ligases, and DNA repair proteins, all of these proteins also share a binding site on the DNA clamp that overlaps with the clamp loader site, ensuring that the clamp will not be removed while any enzyme is still working on the DNA. The activity of the clamp loader requires ATP hydrolysis to "close" the clamp around the DNA.
- Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). Molecular Biology of the Gene 5th ed. Benjamin Cummings: Cold Spring Harbor Laboratory Press.
- Gulbis, J.M., Kelman, Z., Hurwitz, J., O`Donnell, M., Kuriyan, J. (1996). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. Cell 87:297-306.
Protein tertiary structure
|General||Structural domain | Protein folding | Structure determination methods|
|All-α folds:||Helix bundle | Globin fold | Homeodomain fold | Alpha solenoid|
|All-β folds:||Immunoglobulin fold | Beta barrel | Beta-propeller|
|α/β folds:||TIM barrel | Leucine-rich repeat | Flavodoxin fold | Rossmann fold | Thioredoxin fold | Trefoil knot fold|
|α+β folds:||DNA clamp | Ferredoxin fold | Ribonuclease A | SH2-like fold|
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