PCNA (Cyclin, DNA polymerase delta auxiliary protein, Mutagen-sensitive 209 protein, PCNAR, Polymerase delta accessory protein) (APC)

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. [provided by RefSeq, Jul 2008]

PCNA: This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'- 5' exonuclease and 3'-phosphodiesterase, but not apurinic- apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Homotrimer. Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6 and POLDIP2. Interacts with APEX2; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA. Forms a ternary complex with DNTTIP2 and core histone. Interacts with KCTD10 and PPP1R15A. Interacts with POLD1, POLD3 and POLD4. Interacts with BAZ1B; the interaction is direct. Interacts with HLTF and SHPRH. Interacts with NUDT15. Interaction is disrupted in response to UV irradiation and acetylation. Interacts with p21Cip1/p21(CIP1) and CDT1; interacts via their PIP-box which also recruits the DCX(DTL) complex. Interacts with DDX11. Interacts with EGFR; positively regulates PCNA. Interacts with C12orf48/PARI. Interacts with SMARCAD1. Belongs to the PCNA family.

Protein type: DNA replication; Cell cycle regulation

Chromosomal Location of Human Ortholog: 20pter-p12

Cellular Component: nucleoplasm; centrosome; PCNA complex; nuclear replication fork; DNA replication factor C complex; cytoplasm; nucleus

Molecular Function: identical protein binding; protein binding; DNA polymerase processivity factor activity; MutLalpha complex binding; purine-specific mismatch base pair DNA N-glycosylase activity; dinucleotide insertion or deletion binding; receptor tyrosine kinase binding

Biological Process: mismatch repair; positive regulation of deoxyribonuclease activity; heart development; DNA strand elongation during DNA replication; response to lipid; DNA repair; leading strand elongation; telomere maintenance via semi-conservative replication; G1/S-specific transcription in mitotic cell cycle; cell proliferation; bypass DNA synthesis; response to cadmium ion; epithelial cell differentiation; nucleotide-excision repair; base-excision repair; transcription-coupled nucleotide-excision repair; telomere maintenance via recombination; nucleotide-excision repair, DNA gap filling; mitotic cell cycle; telomere maintenance; regulation of DNA replication; G1/S transition of mitotic cell cycle

Disease: Ataxia-telangiectasia-like Disorder 2