GO:0043626 PCNA complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0043626 (PCNA complex) describes the proliferating cell nuclear antigen homotrimer, a ring-shaped DNA sliding clamp that encircles duplex DNA and acts as a central hub for replication, repair, and chromatin regulation.
• The complex is a homotrimer of three PCNA monomers, each with two similar domains arranged head-to-tail to form a ring with a central channel large enough for the DNA double helix.
• PCNA complex functions extend beyond replication to Okazaki fragment processing, translesion DNA synthesis, DNA methylation, chromatin remodeling, and cell cycle regulation.
• PCNA ubiquitination and unloading are tightly controlled by proteins such as ATAD5/Elg1 and BAZ1B, linking the clamp to DNA damage responses and checkpoint activation.
• Dysregulated PCNA complex activity is implicated in cancer, COVID-19 neutrophil hyperactivation, and other proliferative or inflammatory conditions.
• CRISPR-based knockout, point-mutation, knock-in, and overexpression models enable precise dissection of PCNA complex gene functions in health and disease.
Description
The PCNA complex (GO:0043626) is a cellular component defined as a homotrimeric ring formed by three identical proliferating cell nuclear antigen (PCNA) monomers, each comprising two similar domains joined in a head-to-tail arrangement. This ring-like structure encircles the DNA double helix and was originally characterized as the sliding clamp for replicative DNA polymerases and an essential replisome component. Beyond replication, the PCNA complex participates in Okazaki fragment processing, DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling, and cell cycle regulation. Because of its central role in genome maintenance, the PCNA complex is a focal point for researchers studying DNA replication, damage tolerance, and epigenetic inheritance. Its interactions with partner proteins such as ATAD5, BAZ1B, DNMT1, and Polη are critical for coordinating these diverse processes. Understanding the PCNA complex at structural and functional levels is therefore essential for interpreting how cells maintain genomic stability and how this fails in disease.
PCNA complex At A Glance
| GO ID | GO:0043626 |
|---|---|
| GO term | PCNA complex |
| Ontology | cellular_component |
| Synonym | PCNA homotrimer; proliferating cell nuclear antigen complex; sliding clamp |
| Major function | DNA sliding clamp for replicative polymerases; scaffold for DNA repair, translesion synthesis, methylation, and chromatin remodeling |
| Composition | Homotrimer of three PCNA monomers, each with two similar domains |
| Structure | Ring-like with a central channel that accommodates double-stranded DNA |
| Key interacting proteins | ATAD5, BAZ1B, DNMT1, Polη, Elg1/ATAD5 RFC-like complex |
| Associated processes | Okazaki fragment processing, DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling, cell cycle regulation |
What Is GO:0043626?
The PCNA complex is a protein complex composed of three identical PCNA monomers, each containing two similar domains that are joined in a head-to-tail arrangement to form a homotrimer. In solution, it adopts a ring-like structure with a central hole sufficiently large to accommodate the double helix of DNA. Originally characterized as a DNA sliding clamp for replicative DNA polymerases and an essential component of the replisome, it has also been shown to be involved in Okazaki fragment processing, DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling, and cell cycle regulation.
Why Is PCNA complex Important in Cell Biology?
The PCNA complex is a master coordinator of DNA transactions, and its dysfunction is linked to genome instability, cancer, and inflammatory diseases. Because it serves as a platform for numerous proteins, understanding its assembly, regulation, and interactions provides mechanistic insights into replication, repair, and epigenetic inheritance.
• Central to DNA replication as the sliding clamp that tethers polymerases to DNA.
• Essential for DNA repair pathways, including translesion synthesis and mismatch repair.
• Regulates Okazaki fragment processing and chromatin remodeling.
• Involved in DNA methylation through interaction with DNMT1.
• Targeted by regulatory proteins such as ATAD5 and Elg1 for unloading and checkpoint control.
• Implicated in cancer progression and chemoresistance.
• Contributes to neutrophil hyperactivation in COVID-19.
• A key model for studying protein-DNA sliding clamps and ring-shaped complexes.
• Provides a paradigm for post-translational regulation via ubiquitination.
• Enables CRISPR-based functional genomics of replication and repair genes.
What Happens During PCNA complex?
Assembly of the PCNA homotrimer
In simple terms: Three identical PCNA proteins join together to form a ring that can slide along DNA.
The PCNA complex is a homotrimer formed by three identical PCNA monomers, each comprising two similar domains joined in a head-to-tail arrangement. This assembly creates a ring-like structure with a central hole large enough to accommodate the DNA double helix. The trimerization is essential for its function as a sliding clamp.
Loading onto DNA and sliding clamp function
In simple terms: The ring is opened and placed around DNA, where it slides to keep polymerases attached.
The PCNA complex is loaded onto DNA by clamp loader complexes and acts as a sliding clamp for replicative DNA polymerases. It was originally characterized as an essential component of the replisome. The ring slides along duplex DNA, tethering polymerases and other factors to the template.
Okazaki fragment processing and DNA repair
In simple terms: PCNA helps finish copying the lagging strand and fixes DNA damage.
Beyond replication, the PCNA complex is involved in Okazaki fragment processing and multiple DNA repair pathways, including translesion DNA synthesis. It interacts with repair factors and coordinates their access to DNA lesions.
DNA methylation and chromatin remodeling
In simple terms: PCNA also helps control chemical tags on DNA and how DNA is packaged.
The PCNA complex interacts with DNMT1 via its PIP box, linking DNA replication to DNA methylation. It also participates in chromatin remodeling and cell cycle regulation.
Unloading and regulation by ATAD5/Elg1
In simple terms: After DNA is copied, PCNA is removed by a specialized complex.
The yeast PCNA unloader Elg1 RFC-like complex and its human counterpart ATAD5 play roles in eliciting the DNA damage checkpoint and in PCNA unloading. ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair. Alternative clamp loaders/unloaders provide additional layers of regulation.
Key Genes Involved in GO:0043626 PCNA complex
The following genes and proteins are central to the assembly, regulation, and function of the PCNA complex.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PCNA | Forms the homotrimeric sliding clamp | Core component of GO:0043626; target for structural and functional studies |
| ATAD5 | PCNA unloader; interacts with BAZ1B | Regulates PCNA ubiquitination and DNA repair |
| BAZ1B | Modulates ATAD5 interaction | Influences PCNA ubiquitination during DNA repair |
| DNMT1 | DNA methyltransferase; binds PCNA PIP box | Links PCNA to DNA methylation |
| POLH (Polη) | Translesion synthesis polymerase | Forms complex with PCNA for lesion bypass |
| ELG1 (yeast) | PCNA unloader RFC-like complex | Elicits DNA damage checkpoint |
| RFC | Clamp loader | Loads PCNA onto DNA |
| POLD1 | Replicative polymerase | Interacts with PCNA during replication |
| POLE | Replicative polymerase | Interacts with PCNA during replication |
| FEN1 | Okazaki fragment processing | Functions with PCNA in lagging strand maturation |
| LIG1 | DNA ligase I | Works with PCNA in Okazaki fragment processing |
| MSH2 | Mismatch repair | Interacts with PCNA |
| MSH6 | Mismatch repair | Interacts with PCNA |
| CDK1 | Cell cycle regulation | Phosphorylates PCNA-interacting proteins |
| CDK2 | Cell cycle regulation | Phosphorylates PCNA-interacting proteins |
| UBE2D | Ubiquitin-conjugating enzyme | Modifies PCNA ubiquitination |
| USP1 | Deubiquitinase | Regulates PCNA ubiquitination |
How Is PCNA complex Regulated?
The PCNA complex is regulated by post-translational modifications, particularly ubiquitination, which is modulated by ATAD5-BAZ1B interaction during DNA repair. The Elg1/ATAD5 RFC-like complex unloads PCNA from DNA and plays a role in eliciting the DNA damage checkpoint. Alternative clamp loaders/unloaders provide additional regulatory layers. These mechanisms ensure proper timing of PCNA function in replication and repair.
PCNA complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PCNA | Cancer, COVID-19 neutrophil hyperactivation | PCNA knockout or overexpression cell lines |
| ATAD5 | Cancer predisposition, DNA repair defects | ATAD5 knockout cells |
| BAZ1B | DNA repair modulation | BAZ1B point mutants |
| DNMT1 | DNA methylation disorders | DNMT1 PIP box mutants |
| POLH | Translesion synthesis defects | POLH knockout cells |
PCNA complex in cancer
Dysregulation of PCNA complex function is linked to cancer through its roles in DNA replication and repair. The Elg1/ATAD5 complex, which unloads PCNA, is implicated in genome stability and cancer predisposition. Targeting PCNA interactions is a potential therapeutic strategy.
PCNA complex in COVID-19
Cytosolic PCNA orchestrates neutrophil hyperactivation in COVID-19, suggesting a role for the PCNA complex in inflammatory responses. This highlights a non-canonical function of PCNA outside the nucleus.
PCNA complex in DNA repair disorders
Defects in PCNA ubiquitination and unloading, mediated by ATAD5 and BAZ1B, can lead to impaired DNA repair and genomic instability. These pathways are relevant to cancer and developmental disorders.
From PCNA complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of PCNA in replication? | PCNA knockout cell lines |
| How does PCNA ubiquitination affect DNA repair? | Point mutations in PCNA ubiquitination sites |
| How does PCNA interact with DNMT1? | Knock-in of tagged PCNA |
| What is the effect of PCNA overexpression? | PCNA overexpression cell lines |
| How does ATAD5 regulate PCNA unloading? | ATAD5 knockout or knockdown |
| What is the structural basis of PCNA-Polη interaction? | Photo-activatable Ub-PCNA probes |
How to Study the PCNA complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| X-ray crystallography | Atomic structure of PCNA complexes | Studying PCNA-DNMT1 interaction |
| Cryo-EM | Structure of large PCNA complexes | Visualizing PCNA-Polη |
| In vitro loading assays | PCNA loading onto DNA | Testing clamp loaders |
| Ubiquitination assays | PCNA ubiquitination | Studying ATAD5-BAZ1B |
| Fluorescence microscopy | PCNA foci formation | Replication and repair |
| Proteomics | PCNA interactome | Identifying novel partners |
| CRISPR knockout screens | Gene essentiality with PCNA | Identifying synthetic lethality |
| CRISPR knock-in | Tagged PCNA | Live-cell imaging |
Structural biology of the PCNA complex
X-ray crystallography and cryo-EM have revealed the ring-like structure of the PCNA homotrimer and its complexes with partner proteins. Photo-activatable Ub-PCNA probes have provided new structural insights into the Saccharomyces cerevisiae Polη/PCNA complex.
Biochemical assays for PCNA loading and unloading
In vitro assays using purified PCNA, clamp loaders, and DNA substrates measure loading, sliding, and unloading. The yeast PCNA unloader Elg1 RFC-like complex has been studied for its role in checkpoint activation.
Cell-based imaging and proteomics
Fluorescence microscopy and proteomics can visualize PCNA foci and identify interacting proteins. Cytosolic PCNA in neutrophils has been studied in COVID-19.
Genetic screens and CRISPR
CRISPR knockout screens can identify genes that modulate PCNA function and DNA repair. Point mutations and knock-ins allow precise dissection of PCNA post-translational modifications.
How CRISPR Can Be Used to Study GO:0043626 PCNA complex
Knockout
CRISPR knockout of PCNA or its regulators (e.g., ATAD5) can reveal essential roles in replication and repair. Knockout cell lines are valuable for studying PCNA complex function.
Point Mutation
Point mutations in PCNA ubiquitination sites or interaction domains can dissect specific functions without disrupting the entire complex. For example, mutations in the PIP box of DNMT1 affect PCNA binding.
Knock-in
Knock-in of tagged PCNA (e.g., GFP or HA) allows live-cell imaging and proteomic analysis of the PCNA complex. Knock-in of mutant PCNA can model disease-associated variants.
Overexpression
Overexpression of PCNA or its interacting proteins can mimic disease states such as cancer or COVID-19 neutrophil hyperactivation. It is useful for studying gain-of-function effects.
How EDITGENE Supports PCNA complex Research
Researchers studying PCNA complex-related genes often need to determine whether a candidate gene is causally involved in replication, repair, or disease. EDITGENE provides comprehensive CRISPR services to generate precise cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for PCNA complex research.
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
Frequently Asked Questions About PCNA complex
What is the PCNA complex?
The PCNA complex (GO:0043626) is a homotrimeric ring-shaped protein complex that acts as a DNA sliding clamp for replicative polymerases and is involved in DNA repair, translesion synthesis, methylation, and chromatin remodeling.
What genes are involved in the PCNA complex?
Key genes include PCNA, ATAD5, BAZ1B, DNMT1, POLH, and ELG1, among others.
What is the function of PCNA in DNA replication?
PCNA forms a sliding clamp that tethers DNA polymerases to the template, enhancing processivity during replication.
How is PCNA regulated?
PCNA is regulated by ubiquitination, which is modulated by ATAD5-BAZ1B, and by unloading via the Elg1/ATAD5 RFC-like complex.
What diseases are associated with PCNA dysfunction?
PCNA dysfunction is linked to cancer, COVID-19 neutrophil hyperactivation, and DNA repair disorders.
What is the structure of the PCNA complex?
It is a homotrimer with a central channel that accommodates double-stranded DNA, formed by head-to-tail arrangement of monomers.
How can I study PCNA complex using CRISPR?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise functional dissection of PCNA and its partners.
What is the role of ATAD5 in PCNA function?
ATAD5 is a PCNA unloader that interacts with BAZ1B to modulate PCNA ubiquitination during DNA repair.
How does PCNA interact with DNMT1?
PCNA binds DNMT1 via its PIP box, linking DNA replication to DNA methylation.
What methods are used to study the PCNA complex?
Structural biology (X-ray, cryo-EM), biochemical assays, imaging, proteomics, and CRISPR screens are commonly used.
Conclusion
The PCNA complex (GO:0043626) is a fundamental cellular component that coordinates DNA replication, repair, and epigenetic regulation. Its homotrimeric ring structure and dynamic interactions with partner proteins make it a critical hub for genome maintenance. Dysregulation of the PCNA complex is implicated in cancer and inflammatory diseases, underscoring its therapeutic potential. Continued research using advanced CRISPR models will further elucidate its roles and inform targeted interventions.
References
- 1. Kim Y et al.. 2024. ATAD5-BAZ1B interaction modulates PCNA ubiquitination during DNA repair.. Nat Commun 15(1):10496 PMID: 39627214
- 2. Kowalska E et al.. 2018. Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex.. Nucleic Acids Res 46(1):25-41 PMID: 29186524
- 3. Shen S et al.. 2021. Photo-activatable Ub-PCNA probes reveal new structural features of the Saccharomyces cerevisiae Polη/PCNA complex.. Nucleic Acids Res 49(16):9374-9388 PMID: 34390346
- 4. Formiga RO et al.. 2025. Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19.. Proc Natl Acad Sci U S A 122(43):e2503667122 PMID: 41118208
- 5. Sau S et al.. 2019. The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint.. mBio 10(3) PMID: 31186330
- 6. Jimenji T et al.. 2019. Structure of PCNA in complex with DNMT1 PIP box reveals the basis for the molecular mechanism of the interaction.. Biochem Biophys Res Commun 516(2):578-583 PMID: 31235252
- 7. Kubota T et al.. 2013. Is PCNA unloading the central function of the Elg1/ATAD5 replication factor C-like complex?. Cell Cycle 12(16):2570-9 PMID: 23907118
- 8. Kupiec M. 2016. Alternative clamp loaders/unloaders.. FEMS Yeast Res 16(7) PMID: 27664980
