pcna

Proliferating cell nuclear antigen (PCNA) is a conserved, homotrimeric sliding clamp that encircles DNA and acts as a clamp for DNA polymerases during replication and repair. In eukaryotes and archaea, PCNA forms a ring about 8–9 nm in diameter, with each of its three subunits contributing to a central hole through which DNA passes. PCNA serves as a molecular hub, coordinating a wide range of enzymes through interaction motifs known as PIP boxes.

During DNA replication, PCNA is loaded onto primed DNA by the clamp loader RFC in an ATP-dependent reaction. Once loaded, the PCNA ring tethers DNA polymerases to the template, markedly increasing their processivity. It especially promotes processivity of polymerase δ on the lagging strand and polymerase ε on the leading strand, while also coordinating interactions with other replication factors, nucleases, and ligases.

PCNA participates in several DNA repair pathways beyond replication, including base excision repair, nucleotide excision repair, mismatch repair, and translesion synthesis. Its ability to recruit specialized polymerases and repair factors depends on interactions with PIP-box containing proteins and on post-translational modifications that regulate access to damaged sites.

Post-translational modifications of PCNA modulate the DNA damage response. Monoubiquitination at a conserved lysine promotes recruitment of translesion synthesis polymerases, enabling replication across lesions. Polyubiquitination and SUMOylation help direct template switching and fork stabilization, contributing to error-free damage tolerance and fork restart. These modifications are mediated by Rad18 and other E3 ligases, with context-dependent outcomes.

Clinically, PCNA is widely used as a marker of cell proliferation in tissue sections and research. Elevated PCNA expression is observed in proliferating cells and many cancers, and PCNA antibodies are common tools in pathology. The PCNA gene is highly conserved across eukaryotes and archaea, reflecting its essential role in genome maintenance.