PCNA

Proliferating Cell Nuclear Antigen (PCNA) is a protein only expresse in nomal proliferate cells and cancer cells. It is central to both DNA replication and repair. One of the well-established functions for PCNA is its role as the processivity factor for DNA polymerase delta and epsilon. PCNA tethers the polymerase catalytic unit to the DNA template for rapid and processive DNA synthesis. Two forms of PCNA exist in cells: (i) a detergent-insoluble trimeric form stably associated with the replicating forks during S phase and (ii) a soluble form in quiescent cells in G1 and G2 phases. PCNA forms a toroidal trimer in S phase with replication factor-C (RF-C) and DNA in an ATP-dependent manner and enables the loading of DNA polymerase delta and epsilon onto the complex. The close association of PCNA with kinase complexes involved in cell cycle machinery indicates that PCNA has a regulatory role in cell cycle progression. PCNA also participates in the processing of branched intermediates that arise during the lagging strand DNA synthesis.

PCNA Related Areas

 

PCNA Alternative Names

MGC8367[Homo sapiens]

RP23-33N15.1[Mus musculus]

Summaries for PCNA

Entrez Gene summary for PCNA:

The protein encoded by PCNA 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 PCNA 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 PCNA gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

Wikipedia summary for PCNA:

Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome. It is an example of a DNA clamp. The protein encoded by this PCNA gene is found in the nucleus and is a cofactor of DNA polymerase delta.

Human PCNA Protein General Information

 

• Protein names: Proliferating cell nuclear antigen, Short name=PCNA
• Sequence length: 261 AA.
• Sequence similarities: PCNA belongs to the PCNA family.
• Post-translational modification: Upon methyl methanesulfonate-induced DNA damage, mono-ubiquitinated by the UBE2B-RAD18 complex on Lys-164. This induces non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH, which is required for DNA repair. 'Lys-63' polyubiquitination prevents genomic instability on DNA damage. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis.
• Subunit structure: PCNA 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 CDKN1A/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.
• Subcellular location: Nucleus. Note: Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase. Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.
• Miscellaneous: Antibodies against PCNA are present in sera from patients with systemic lupus erythematosus.

General information above from UniProt

Function for PCNA Protein

UniProtKB:

PCNA 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. PCNA induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. It has to be loaded onto DNA in order to be able to stimulate APEX2.

Genatlas:

• PCNA is involved in the control of DNA replication by increasing the polymerase processsibility during elongation of the loading strand
• exonuclease activity linked to the RAD6 pathway of post-replicative DNA repair
• PCNA is the major regulator of chromatin assembly during DNA repair
• PCNA is central matchmaker for replication-linked functions, is also crucially involved in the establishment of cohesion in S phase
• mono-ubiquitination of PCNA mediates the switch from replicative DNA polymerases to polymerases specialised for translesion synthesis (modification necessary for the survival of cells after UV-irradiation) (Pubmed 19221475)
• PCNA functions as a sliding clamp for the replicative polymerase Poldelta, also interacts with the three TLS (Translesion synthesis) polymerases (Pubmed 19208623)
• PCNA promotes cancer survival by immune evasion through inhibition of NCR2-mediated NK cell attack (Pubmed 22021614)

Homology for human PCNA

• homolog to murine Pcna
• homolog to C.elegans pcn-1