PCNA
GeneName
PCNA
Summary
PCNA, also known as cyclin or proliferating cell nuclear antigen, is a 29 kDa protein that plays a crucial role in DNA replication and repair. It is primarily localised in the nucleus, where it forms a homotrimeric ring structure that encircles DNA, acting as a processivity factor for DNA polymerase during leading strand synthesis. PCNA is involved in various cellular processes including chromatin organisation, mismatch repair, and base-excision repair. It also interacts with numerous proteins, such as histone acetyltransferases and DNA polymerases, to facilitate its functions in DNA metabolism and cellular responses to DNA damage.
Importance
PCNA is relevant to: - DNA replication and repair mechanisms, making it a target for cancer research and therapeutic interventions - Cellular responses to oxidative stress and DNA damage, which are critical in understanding ageing and disease processes - Regulation of cell cycle progression and differentiation, particularly in rapidly dividing cells such as those in the epithelial and germ cell lineages - Its potential as a biomarker for cell proliferation in various cancers, aiding in diagnosis and treatment strategies
Top Products
For researchers investigating PCNA, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the highly regarded Anti-PCNA antibody [PC10] (ab29), a well-cited monoclonal antibody with 917 citations, demonstrating its reliability in Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). This antibody has established itself as a trusted tool in the field.Additionally, we offer the recombinant antibody, Anti-PCNA antibody [EPR3821] (ab92552), which has been validated for use in WB, IHC, ICC, flow cytometry (FC), and immunoprecipitation (IP). With 567 citations, this recombinant product provides the batch-to-batch consistency that researchers often seek. Together, these antibodies provide robust options for studying PCNA in various experimental contexts. The Human PCNA ELISA Kit (ab196270), supported by 3 citations, is an excellent option for researchers looking to accurately measure PCNA levels in their samples.
Abcam Product Citation Summary
The data indicates a significant focus on the role of PCNA in various cancer contexts, particularly in human cell lines and tissues. The use of multiple antibodies in Western blotting and immunohistochemistry highlights the importance of PCNA as a marker for cell proliferation and tumor growth. Studies span a range of cancer types, including glioblastoma, cervical cancer, and hepatocellular carcinoma, suggesting that PCNA is a critical target for understanding cancer biology and potential therapeutic interventions.
Abcam Product Citation Table
Function
Confers DNA tethering and processivity to DNA polymerases and other proteins (PubMed:24695737, PubMed:24939902, PubMed:35585232). Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of DNA replication by increasing the polymerases' processivity during elongation of the leading strand (PubMed:35585232). 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. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902). Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion (PubMed:24695737).
Involvement in disease
Ataxia-telangiectasia-like disorder 2
ATLD2
A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA.
Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation (PubMed:19419956, PubMed:24939902). Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner (PubMed:24939902). Acetylation disrupts interaction with NUDT15 and promotes degradation (PubMed:19419956).
Ubiquitinated (PubMed:20227374, PubMed:24939902). Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires 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. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. 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. Sumoylated during S phase.
Methylated on glutamate residues by DCPH1/C6orf211.
Sequence Similarities
Belongs to the PCNA family.
Cellular localization
- Nucleus
- Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage (PubMed:24939902). Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase (PubMed:15543136). Co-localizes with SMARCA5/SNF2H and BAZ1B/WSTF at replication foci during S phase (PubMed:15543136). Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.
Alternative names
DNA sliding clamp PCNA, Cyclin, Proliferating cell nuclear antigen, PCNA