Replication factor C subunit 1 (RFC1)

Replication factor C subunit 1 (RFC1) is the large (140 kDa) subunit of the replication factor C complex, a heteropentameric protein essential for eukaryotic DNA replication and repair[3][5][2]. As a DNA-dependent ATPase, RFC1 cooperates with DNA polymerases and loads proliferating cell nuclear antigen (PCNA) onto DNA, facilitating the formation of a sliding clamp required for high-fidelity DNA synthesis[1][2][7][5]. This protein also binds both single- and double-stranded DNA, promotes elongation of DNA strands during replication, and functions in telomere maintenance, mismatch repair, base excision repair, and cell cycle checkpoint signaling[1][5][7]. RFC1 genetic mutations, particularly biallelic pentanucleotide repeat expansions (notably “AAGGG”) in an intronic Alu element, are a recognized cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and related neurological phenotypes[3][1]. RFC1 function is vital for genome stability, but current evidence does not indicate it as a direct therapeutic target for small molecules or drugs, and it is not associated with increased cancer risk in affected individuals with repeat expansions[1]. RFC1 may influence transcriptional programs through protein–protein interactions (e.g., with NF-κB/RelA, HDAC1)[2]; however, its core cellular functionality is as a DNA clamp loader in conjunction with the PCNA sliding clamp, serving as an accessory factor for DNA polymerases. Note: RFC1 is not considered a therapeutic target such as a receptor, enzyme, or transporter suitable for direct pharmacological modulation. It is, however, a critical gene important for DNA replication and repair and is best recognized as a biomarker in neurogenetic diagnosis rather than as a drug target[1][3][5][2].

Other names

Replication factor C 140 kDa subunitRFC140Activator 1 large subunitActivator 1 subunit 1DNA-binding protein PO-GAMHC binding factor betaCANVAS (in context of associated disease)PO-GARECC1MHCBFBA1 140 kDa subunitRF-C 140 kDa subunit