Replication factor C (RFC) is an essential DNA polymerase accessory protein that is required for numerous aspects of DNA metabolism, including DNA replication, DNA repair and telomere metabolism. RFC is a heteropentameric complex that recognizes a primer on a template DNA, binds to a primer terminus and loads proliferating cell nuclear antigen (PCNA) onto DNA at primer-template junctions in an ATP-dependent reaction. All five of the RFC subunits share a set of related sequences (RFC boxes) that include nucleotide-binding consensus sequences. Four of the five RFC genes (including RFC1, RFC2, RFC3 and RFC4) have consensus ATP-binding motifs. The small RFC proteins, RFC2, RFC3, RFC4 and RFC5, interact with Rad24, whereas the RFC1 subunit does not. RFC1 is a substrate for caspase-3 in vitro and is cleaved by a caspase-3-like protease during FAS-mediated apoptosis. In addition, phosphorylation of the PCNA binding domain of RFC1 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibits DNA synthesis. The human RFC1 gene maps to chromosome 4p14 and encodes the RFC1 subunit.