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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PCNA
proliferating cell nuclear antigen
Chromosome 20 · 20p12.3
NCBI Gene: 5111Ensembl: ENSG00000132646.12HGNC: HGNC:8729UniProt: P12004
991PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
purine-specific mismatch base pair DNA N-glycosylase activityhistone acetyltransferase bindingidentical protein bindingprotein-containing complex bindingataxia-telangiectasia-like disorderneurodegenerative diseasehepatocellular carcinomaneoplasm
✦AI Summary

PCNA (proliferating cell nuclear antigen) is a homotrimeric ring-shaped processivity factor essential for DNA replication and repair 1. It encircles DNA and slides along it, tethering DNA polymerases delta and epsilon to increase their processivity during leading strand synthesis 1. PCNA serves as a dynamic molecular hub that coordinates replication with DNA damage response by recruiting repair proteins through PCNA-interacting protein box (PIP-box) motifs 1. Following replication fork stalling, monoubiquitination of PCNA at lysine 164 recruits translesion synthesis polymerases (REV1, POLζ) for error-prone lesion bypass 2. Alternatively, K63-linked polyubiquitination engages error-free homologous recombination pathways 3. PCNA K164 ubiquitination also promotes FANCD2-dependent mitotic DNA synthesis to resolve under-replicated regions 3. After fork restart, ATAD5-containing complexes actively de-ubiquitinate PCNA to restore replication fidelity 4, with BAZ1B modulating timely de-ubiquitination to prevent premature resumption 5. Dysregulation of PCNA cycling impairs genome stability; checkpoint failure causes PCNA/RFC sequestration by excess DNA synthesis, triggering HLTF-mediated fork collapse 6. These mechanisms underscore PCNA's critical role in coordinating replication fork progression with DNA damage tolerance.

Sources cited
1
PCNA forms homotrimeric ring embracing DNA, anchors polymerases through PIP-box interactions
PMID: 32276417
2
PCNA monoubiquitination recruits REV1 and POLζ translesion polymerases for gap filling
PMID: 34624216
3
PCNA K164 ubiquitination activates FANCD2-dependent mitotic DNA synthesis
PMID: 38060446
4
ATAD5-containing complexes actively de-ubiquitinate and unload PCNA from DNA
PMID: 38485608
5
BAZ1B modulates ATAD5-mediated PCNA de-ubiquitination to prevent premature replication resumption
PMID: 39627214
6
Checkpoint failure causes PCNA/RFC sequestration leading to HLTF-mediated replication fork collapse
PMID: 40578346
Disease Associationsⓘ21
ataxia-telangiectasia-like disorderOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.19Weak
hepatocellular carcinomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
infectionOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
oral squamous cell carcinomaOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Suggestive
diabetes mellitusOpen Targets
0.10Suggestive
esophageal squamous cell carcinomaOpen Targets
0.09Suggestive
osteosarcomaOpen Targets
0.09Suggestive
cervical cancerOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
COVID-19Open Targets
0.08Suggestive
sarcomaOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
Pallister-Hall syndromeOpen Targets
0.07Suggestive
squamous cell carcinomaOpen Targets
0.07Suggestive
azoospermiaOpen Targets
0.07Suggestive
Ataxia-telangiectasia-like disorder 2UniProt
Pathogenic Variants1
NM_182649.2(PCNA):c.443G>C (p.Cys148Ser)Likely pathogenic
Ataxia-telangiectasia-like disorder 2
★★☆☆2025→ Residue 148
View on ClinVar ↗
Related Genes
FEN1Protein interaction100%MSH6Protein interaction100%LIG1Protein interaction100%MLH1Protein interaction100%RFC5Protein interaction100%RFC1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
30%
Lung
10%
Ovary
10%
Heart
9%
Liver
9%
Gene Interaction Network
Click a node to explore
PCNAFEN1MSH6LIG1MLH1RFC5RFC1
PROTEIN STRUCTURE
Preparing viewer…
PDB1U7B · 1.88 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.18 [0.09–0.42]
RankingsWhere PCNA stands among ~20K protein-coding genes
  • #162of 20,598
    Most Researched991 · top 1%
  • #4,603of 5,498
    Most Pathogenic Variants1
  • #2,210of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedPCNA
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Human PCNA Structure, Function and Interactions.
PMID: 32276417
Biomolecules · 2020
1.00
2
RAD18 O-GlcNAcylation promotes translesion DNA synthesis and homologous recombination repair.
PMID: 38719812
Cell Death Dis · 2024
0.90
3
Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells.
PMID: 34624216
Mol Cell · 2021
0.90
4
Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2.
PMID: 39578540
EMBO J · 2025
0.88
5
Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells.
PMID: 39291733
Nucleic Acids Res · 2024
0.86