PCNA

Description

The PCNA (proliferating cell nuclear antigen) is a protein-coding gene located on chromosome 20.

Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics. Many proteins interact with PCNA via the two known PCNA-interacting motifs PCNA-interacting peptide (PIP) box and AlkB homologue 2 PCNA interacting motif (APIM). Proteins binding to PCNA via the PIP-box are mainly involved in DNA replication whereas proteins binding to PCNA via APIM are mainly important in the context of genotoxic stress.

== Function == The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. PCNA is also found in archaea, as a processivity factor of polD, the single multi-functional DNA polymerase in this domain of life.

PCNA is an auxiliary protein of DNA polymerase delta and epsilon, involved in eukaryotic DNA replication by enhancing the polymerase's processivity during elongation of the leading strand. It stimulates the 3'-5' exonuclease and 3'-phosphodiesterase activities, but not apurinic-apyrimidinic (AP) endonuclease activity. PCNA must be loaded onto DNA to stimulate APEX2. It plays a key role in DNA damage response (DDR) by coordinating DNA replication with DNA repair and DNA damage tolerance pathways. As a loading platform, it recruits DDR proteins, enabling completion of DNA replication after damage and promoting postreplication repair. Monoubiquitinated PCNA recruits translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in the error-free pathway and uses recombination mechanisms to synthesize across the lesion.

PCNA is also known as ATLD2.

Associated Diseases

• Ataxia-telangiectasia-like disorder 2
• PCNA-related progressive neurodegenerative photosensitivity syndrome