RFC4

The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 37 kD subunit. This subunit forms a core complex with the 36 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding the same protein have been reported.

Radioresistance of esophageal squamous carcinoma cells is a critical factor leading to treatment failure and recurrence. RFC4 expression is significantly upregulated in esophageal squamous carcinoma cell tissues and cells, particularly in cases that are radioresistant. RFC4 plays a role in conferring radioresistance to esophageal squamous cell carcinoma by bolstering repair of DNA damage. Thus RFC4 is a promising therapeutic target for combating radioresistance in esophageal squamous cell carcinoma.

RFC4 has been shown to interact with:

• BRD4,
• CHTF18,
• PCNA,
• RFC2,
• RFC3, and
• RFC5.