clamploader

ClampLoader is a protein complex that loads sliding clamps onto DNA to enable high-processivity DNA synthesis during replication and repair. Sliding clamps encircle DNA and tether DNA polymerases to the template, allowing rapid, processive synthesis. ClampLoader harnesses ATP binding and hydrolysis to open the clamp, place it around DNA, and release the loaded clamp for polymerase engagement.

In bacteria, the clamp loader is the gamma complex of the DNA polymerase III holoenzyme. Its typical composition includes gamma (and its longer form tau in some contexts), delta, delta', and the accessory subunits chi and psi. This complex binds the beta sliding clamp and primer–template junctions, uses ATP hydrolysis to open the clamp ring, and then hands the loaded clamp to the polymerase core. The tau-containing forms can also link two polymerase cores to the clamp loader, coordinating synthesis on the leading and lagging strands.

In archaea and eukaryotes, the clamp loader is the Replication Factor C (RFC) complex. RFC consists of five subunits (RFC1–RFC5) and loads the PCNA sliding clamp in a manner analogous to bacterial systems, using ATP to open PCNA and seal it around DNA. PCNA then associates with DNA polymerases delta and epsilon, among others, to sustain replication and participate in DNA repair pathways.

Common features include ATPase activity within the clamp loader, transient interaction with the sliding clamp and DNA, and release of the loaded clamp to enable polymerase activity. Clamp loaders are essential for genome duplication and maintenance, making them central to cellular replication fidelity.