General Information about PCNA Protein
PCNA protein also known as proliferating cell nuclear antigen is a DNA clamp and a catalyzer of DNA polymerase delta. PCNA protein is essential for the replication of eukaryotic cells. The protein is a homotrimer which increase it processivity towards DNA polymerase delta. PCNA protein encircles the DNA and acts as a scaffold to recruit proteins implicated in DNA repair, DNA chromatin remodeling, DNA replication and is involved in epigenetics. PCNA protein contains two PCNA-interacting motifs, the PCNA-interacting peptide (PIP) bx and AlkB homologue 2 PCNA interacting motif (APIM). The proteins that interact with PCNA via PIP box are mainly involved in DNA replication. On the other hand, the proteins that bind to APIM box of PCNA protein are believed to be involved in genotoxic stress. The PCNA protein is ubiquitinated following DNA damage. The protein is also involved in RAD6-dependent DNA repair pathway.
PCNA protein holds DNA polymerase attached to DNA. The former is involved in re-synthesis of damaged DNA that has been excised. As such, PCNA protein is involved in both DNA repair and DNA synthesis. Furthermore, the protein is implicated in DNA damage tolerance pathways which is also known as post-replication repair or PRR. PRR consists of two pathways; (1) a translesion pathway which is carried out special DNA polymerases that incorporate DNA bases into their active sites and (2) a template switch pathway which involves the recruitment of the homologous recombination machinery. PCNA protein activates these pathways depending on what is required for the cell. PCNA protein is ubiquinated post-translationally. Mono-ubiquitin on lysine 164 leads to PCNA activation of translesion pathways. Extension of the mono-ubiquitin by a non-canonical lysine-63-linked poly-ubiquitin chain is believed to be implicated in the activation of the template switch pathway. However, sumoylation of PCNA lysine 164 inhibts the template switch pathway. The expression of PCNA protein are regulated by E2F transcriptor factor-containing complex.