Clamping down on clamps and clamp loaders

Abstract

DNA transactions such as DNA replication and DNA repair require the concerted action of many enzymes, together with other proteins and non‐protein cofactors. Among them three main accessory proteins, replication factor C (RF‐C), proliferating‐cell nuclear antigen (PCNA) and replication protein A (RP‐A), are essential for accurate and processive DNA synthesis by DNA polymerases. RF‐C is a complex consisting of five polypeptides with distinct functions. RF‐C can bind to a template‐primer junction and, in the presence of ATP, load the PCNA clamp onto DNA, thereby recruiting DNA polymerases to the site of DNA synthesis. RF‐C not only acts as a clamp loader in DNA replication and DNA repair, but there is some evidence that it could be involved in several other processes such as transcription, S‐phase checkpoint regulation, apoptosis, differentiation and telomere‐length regulation.