Anti-PCNA monoclonal antibody, clone PC10

Proliferating cell nuclear antigen (PCNA) is a highly conserved protein that exists widely in eukaryotes and archaea, and it has significant biological functions. PCNA was originally identified as an auxiliary factor of DNA polymerase δ, primarily responsible for the continuity of DNA synthesis. However, with further research, it has become clear that PCNA's functions extend far beyond DNA replication, as it also plays a role in chromatin remodeling, DNA repair, cell cycle regulation, and various other biological processes. Its multifunctionality and complexity make it a core regulatory factor in important mechanisms such as cell proliferation, genomic stability, and cellular stress responses. The discovery of PCNA dates back more than 30 years, when it was first identified as an autoantigen in the serum of patients with systemic lupus erythematosus. Subsequently, a 36 kDa protein associated with cell cycle changes was identified and named "cyclin." Further research revealed that PCNA and cyclin were actually the same protein, and its expression was closely linked to cell proliferation and tumorigenesis. This finding established PCNA as a crucial marker for cell proliferation, making it a key molecule in the study of cell proliferation, DNA damage repair, and tumor biology. The PCNA gene has been identified in various organisms, including animals, yeast, and higher plants, demonstrating a high level of conservation. PCNA from yeast and Drosophila can functionally replace mammalian PCNA in DNA replication, and plant PCNA can stimulate the activity of human DNA polymerase δ. These studies indicate that PCNA's role in DNA replication has remained highly consistent throughout evolution, highlighting its critical function as a sliding clamp in DNA synthesis. PCNA interacts with DNA polymerase and other replication-related proteins to form stable complexes that ensure the efficiency and accuracy of DNA synthesis. PCNA belongs to the sliding clamp family, which includes the β subunit of Escherichia coli DNA polymerase III and the gp45 protein of bacteriophage T4. Through electron microscopy and X-ray diffraction analysis, scientists confirmed the ring-shaped structure of PCNA, which is similar to the β subunit of DNA polymerase. This structure allows PCNA to freely slide along the DNA molecule, ensuring the smooth progression of DNA replication. PCNA's trimeric ring structure further demonstrates its key role in DNA replication, coordinating DNA synthesis through its interaction with replication fork-associated proteins. The ring structure allows PCNA to flexibly bind during replication and repair processes, with the positively charged region on its inner surface being crucial for interacting with DNA. PCNA can bind to multiple proteins simultaneously and regulate DNA replication and repair through its various functional domains, such as the interdomain connecting loop (IDCL). IDCL is essential for PCNA's biological activity, particularly its interactions with DNA polymerase δ, primase, and other replication factors.

Figure 1. Structural features of PCNA (Source: Park SY, et al., 2016)

In DNA replication, PCNA's role is not limited to maintaining the stability of DNA polymerase; it also participates in key steps such as replication initiation and Okazaki fragment maturation. During replication initiation, PCNA assists in loading DNA polymerase δ and ε, ensuring the continuity of DNA synthesis. PCNA's binding to the primer end is an important signal for the transition from DNA polymerase α to δ or ε, a process that ensures synchronized DNA synthesis on the leading and lagging strands. Especially on the lagging strand, PCNA works closely with DNA polymerase δ to complete the synthesis of discontinuous Okazaki fragments and helps remove primers and ligate fragments through its interactions with Fen1 and DNA ligase. PCNA also plays a critical role in DNA repair, particularly in the repair processes following DNA damage. Different DNA repair systems, such as base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR), all involve PCNA. In BER, PCNA assists DNA polymerase δ or β in synthesizing DNA and collaborates with Fen1 and DNA ligase to complete the repair of damaged sites. PCNA also plays a role in loading repair proteins and promoting DNA synthesis in NER and MMR, ensuring the accuracy and efficiency of the repair process.

Figure 2. Model of eukaryotic DNA replication (Source: Strzalka W,et al., 2011)

Translesion synthesis (TLS) is another important process dependent on PCNA. When the replication fork encounters DNA damage, PCNA interacts with specialized TLS polymerases, enabling these polymerases to bypass the damaged site and continue DNA synthesis. During this process, the monoubiquitination of PCNA is a crucial regulatory event that activates TLS polymerases and ensures the continuation of DNA synthesis. Although TLS polymerases have lower accuracy, PCNA regulates their activity through specific protein-protein interactions to prevent mutations caused by errors. Although the role of PCNA in DNA repair in plants is not fully understood, evidence suggests that plant PCNA may function similarly to its counterparts in animals and yeast. Particularly, plant DNA polymerases, Fen1, and other repair-related proteins have been shown to interact with PCNA, indicating that PCNA likely plays a role in plant DNA repair through these interactions, although the exact mechanisms require further investigation. In conclusion, PCNA is a crucial regulatory factor in cell proliferation and genomic stability. Its multifunctionality in DNA replication, repair, and cell cycle control makes it a core focus of modern molecular biology research. Future studies on PCNA and its related proteins will help further reveal the complexity of genome maintenance mechanisms and may provide new targets and strategies for disease treatment.

Anti-proliferating cell nuclear antigen antibody
PCNA monoclonal antibody
PC10 antibody
Anti-PCNA antibody