Affinage

PCNA

DNA sliding clamp PCNA · UniProt P12004

Round 2 corrected
Length
261 aa
Mass
28.8 kDa
Annotated
2026-04-29
130 papers in source corpus 48 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PCNA is a homotrimeric DNA sliding clamp that serves as a central coordinator of DNA replication, repair, and chromatin maintenance by providing a processivity platform for DNA polymerase δ (stimulating nucleotide incorporation rate >10-fold) and by recruiting diverse partners through conserved PIP-box and APIM interaction motifs on its interdomain connector loop (PMID:30605530, PMID:19736315, PMID:8861913). PCNA orchestrates Okazaki fragment maturation through a toolbelt mechanism in which FEN1 and DNA Ligase 1 occupy separate PCNA monomers for sequential substrate handoff, coordinates mismatch repair by acting as both a strand-discrimination signal and a retention platform for MutSα, and facilitates translesion synthesis through monoubiquitination at K164 by RAD6/RAD18, which triggers recruitment of Y-family polymerases bearing ubiquitin-binding domains (PMID:36539424, PMID:27402201, PMID:12226657, PMID:15149598, PMID:16357261). Additional post-translational modifications—including K63-linked polyubiquitination for error-free damage bypass, SUMO conjugation that recruits the anti-recombinase Srs2, Y211 phosphorylation by EGFR that stabilizes chromatin-bound PCNA and modulates MMR, K248 methylation by SETD8 that enhances FEN1 interaction, and acetylation by CBP/p300 that promotes PCNA removal and degradation after NER—enable context-dependent regulation of partner access and clamp dynamics (PMID:12226657, PMID:22382979, PMID:17115032, PMID:25825764, PMID:22556262, PMID:24939902). A hypomorphic PCNA-S228I mutation causes a human DNA repair disorder featuring neurodegeneration and photosensitivity by selectively disrupting interactions with FEN1 and DNA Ligase 1 (PMID:24911150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Establishing PCNA as a regulated replication factor: p21 and GADD45 were shown to directly bind PCNA and functionally modulate DNA replication and repair, revealing PCNA as a protein–protein interaction hub rather than a passive processivity clamp.

    Evidence In vitro SV40 replication reconstitution (p21 inhibition), co-IP/yeast two-hybrid/repair assays (GADD45 binding and repair stimulation)

    PMID:7911228 PMID:7973727

    Open questions at the time
    • Structural basis of GADD45–PCNA interaction unresolved
    • How p21 and GADD45 compete or cooperate on the same PCNA surface was unknown
  2. 1996 High

    The crystal structure of PCNA–p21 peptide defined the interdomain connector loop (IDCL) as the primary partner-docking site and established the structural logic of the PIP-box interaction motif, explaining how a single surface mediates mutually exclusive partner binding.

    Evidence X-ray crystallography at 2.6 Å of human PCNA–p21 complex

    PMID:8861913

    Open questions at the time
    • How partners beyond p21 are prioritized on the IDCL was unclear
    • Full-length partner complex structures were lacking
  3. 1996 High

    PCNA was found to function in mismatch repair upstream of DNA resynthesis, interacting with MLH1 and MSH2 and establishing its role as a repair scaffold beyond replication.

    Evidence Yeast two-hybrid, genetic epistasis, in vitro MMR assay with p21 peptide inhibition/rescue

    PMID:8858149

    Open questions at the time
    • Whether PCNA serves as the strand-discrimination signal was unresolved
    • Mechanism of PCNA–MutL coupling not defined
  4. 1997 High

    Demonstration that DNMT1 binds PCNA at replication foci via a PIP-like motif extended PCNA's scaffold role to epigenetic maintenance, linking DNA replication to maintenance methylation.

    Evidence Co-IP, replication foci imaging, peptide competition with p21

    PMID:9302295

    Open questions at the time
    • Whether PCNA binding is sufficient for DNMT1 targeting or whether additional cues are needed was unknown
  5. 2000 High

    FEN1 was shown to interact with PCNA through two distinct binding modes (solution vs. DNA-loaded), and disruption of this interaction caused replication/repair defects, establishing PCNA–FEN1 coupling as essential for Okazaki fragment maturation.

    Evidence PCNA mutant analysis, in vitro FEN1 stimulation assay, in vivo phenotyping in yeast

    PMID:10899134

    Open questions at the time
    • Whether PCNA simultaneously accommodates FEN1 and Ligase 1 (toolbelt model) was untested
  6. 2002 High

    The discovery that PCNA K164 is the shared site for monoubiquitination (Rad6/Rad18), K63-polyubiquitination (Mms2/Ubc13/Rad5), and sumoylation (Ubc9) established post-translational modification as the master switch for channeling PCNA between damage tolerance pathways.

    Evidence Biochemical modification assays, genetic epistasis in yeast, mass spectrometry, conservation in human cells

    PMID:12226657

    Open questions at the time
    • How monoubiquitin recruits specific TLS polymerases was unknown
    • The deubiquitinase reversing K164 ubiquitination was unidentified
  7. 2004 High

    Monoubiquitinated PCNA was shown to specifically recruit DNA polymerase η for the replicative-to-TLS polymerase switch after UV, with RAD18 guiding the process through dual interactions with PCNA and polη.

    Evidence Co-IP, UV irradiation assays, domain mapping, in vitro ubiquitination with purified proteins, RAD18-knockout cells

    PMID:15149598 PMID:15359278

    Open questions at the time
    • Whether multiple TLS polymerases can simultaneously occupy PCNA was unknown
    • Structural basis of ubiquitin–polη UBZ interaction not determined
  8. 2005 High

    USP1 was identified as the deubiquitinase that reverses PCNA monoubiquitination; UV-triggered USP1 autocleavage allows ubiquitinated PCNA to accumulate, providing a UV-responsive on/off switch for TLS activation.

    Evidence In vitro DUB assay, UV Western blot, autocleavage mapping, RNAi knockdown

    PMID:16531995

    Open questions at the time
    • How USP1 is regenerated after UV recovery was not defined
    • Whether other DUBs contribute to PCNA deubiquitination in specific contexts was unknown
  9. 2005 High

    Y-family TLS polymerases were shown to require ubiquitin-binding domains (UBM/UBZ) for interaction with monoubiquitinated PCNA and localization to replication factories, with the UBZ of polη essential for correcting the XP-V UV phenotype.

    Evidence Domain mutagenesis, binding assays, focus formation, XP-V cell complementation

    PMID:16357261

    Open questions at the time
    • How polymerase switching back from TLS to replicative synthesis occurs was not established
  10. 2005 High

    PCNA dynamics were measured in living cells, showing rapid exchange at replication foci but prolonged retention at UV-damaged sites in a K164 ubiquitination-dependent manner, linking PCNA modification to its physical residence time on chromatin.

    Evidence FRAP with GFP-PCNA, UV laser damage, NER-mutant and K164R-mutant cell lines

    PMID:16227586

    Open questions at the time
    • The relationship between PCNA residence time and specific repair pathway activation was correlative
  11. 2006 High

    Y211 phosphorylation by nuclear EGFR was identified as a stabilizer of chromatin-bound PCNA, and PCNA K164 modifications were linked to immunoglobulin somatic hypermutation, expanding PCNA's regulatory scope to both growth factor signaling and adaptive immunity.

    Evidence In vivo phosphorylation/MS/chromatin fractionation (Y211); PCNA-K164R knock-in in DT40 cells with Ig sequencing (SHM)

    PMID:17105346 PMID:17115032

    Open questions at the time
    • Whether Y211 phosphorylation and K164 ubiquitination cross-regulate each other was unknown
    • Structural impact of Y211 phosphorylation on partner binding undetermined
  12. 2008 High

    PCNA sumoylation was shown to be stimulated by DNA loading itself, implying a conformational change upon ring closure; Chk1/Claspin/Timeless were found to regulate RAD18-dependent PCNA ubiquitination, integrating checkpoint signaling with PCNA modification.

    Evidence In vitro sumoylation reconstitution plus in vivo genetic analysis (sumoylation); RNAi epistasis with chromatin fractionation (Chk1/Claspin pathway)

    PMID:18451105 PMID:18701921

    Open questions at the time
    • Nature of the conformational change upon DNA loading not structurally resolved
    • Direct mechanism by which Claspin promotes RAD18 chromatin binding unclear
  13. 2009 High

    The APIM motif was identified as a second, PIP-box-independent PCNA-interaction motif present in >200 proteins, broadening the known PCNA interactome; separately, a novel ubiquitination site at K107 responsive to ligation defects was discovered.

    Evidence Pull-down/co-localization/cell-penetrating peptide assay (APIM); yeast genetics/Western blot with K107R mutant/human cell validation (K107 ubiquitination)

    PMID:19736315 PMID:20010813

    Open questions at the time
    • Structural basis of APIM–PCNA interaction not determined
    • E3 ligase and functional consequences of K107 ubiquitination in human cells incompletely defined
  14. 2011 High

    CRL4(Cdt2) was shown to couple PCNA binding via PIP degrons to proteasomal destruction of Cdt1, p21, and Set8 on chromatin, establishing PCNA as the trigger for S-phase-specific proteolysis that prevents rereplication. Separately, FEN1-PCNA interaction was validated in vivo via knock-in mice where its loss caused aneuploidy and cancer.

    Evidence Biochemical reconstitution of CRL4-dependent degradation; FEN1 FFAA knock-in mice with chromosomal and cancer phenotyping

    PMID:21383776 PMID:21828267

    Open questions at the time
    • How CRL4(Cdt2) distinguishes chromatin-bound from free PCNA–substrate complexes at molecular level was unclear
  15. 2012 High

    SETD8-mediated methylation of PCNA at K248 was shown to enhance FEN1 interaction and Okazaki fragment maturation, and the Srs2 anti-recombinase was structurally demonstrated to recognize SUMO-PCNA via tandem PCNA- and SUMO-binding motifs, explaining the specificity of recombination suppression at replication forks.

    Evidence In vitro methylation/K248R mutant/Okazaki fragment assay (SETD8); crystal structure/NMR/biochemical and yeast functional analysis (Srs2–SUMO-PCNA)

    PMID:22382979 PMID:22556262

    Open questions at the time
    • Whether K248 methylation is dynamically regulated during S phase was unknown
    • Whether Srs2 and other SUMO-PCNA readers compete in vivo was untested
  16. 2014 High

    CBP/p300-mediated acetylation of PCNA at K13/14/77/80 was shown to promote PCNA unloading and degradation after NER, providing a mechanism for post-repair clamp clearance. The human PCNA-S228I mutation was identified as causing a DNA repair disorder, directly linking PCNA partner interactions (FEN1, Ligase 1) to neurodegeneration and photosensitivity.

    Evidence In vitro acetylation/lysine mutant cell lines/UV sensitivity (acetylation); patient cell analysis/protein interaction/UV survival assays (S228I disease)

    PMID:24911150 PMID:24939902

    Open questions at the time
    • Whether acetylation-dependent unloading uses the same ATAD5/Elg1 pathway was untested
    • Full clinical spectrum and genotype–phenotype relationship of PCNA-associated disease incompletely characterized
  17. 2015 High

    Y211 phosphorylation by EGFR was further shown to directly inhibit MMR by altering PCNA interactions with MutSα/β and impairing MutLα endonuclease activation, establishing a molecular mechanism linking EGFR signaling to mismatch repair suppression and replication infidelity.

    Evidence In vitro MMR and nucleotide incorporation assays with phospho-PCNA mutants, co-IP

    PMID:25825764

    Open questions at the time
    • In vivo contribution of EGFR-dependent PCNA phosphorylation to tumorigenesis not formally tested in animal models
  18. 2016 High

    Multiple studies converged to establish PCNA as a toolbelt and strand-discrimination platform: MutSα inhibits PCNA unloading to extend the MMR-permissive window using PCNA itself as the nascent-strand marker; single-molecule imaging revealed simultaneous TLS polymerase occupancy on PCNA; FANCM, TRAIP, and HUWE1 were identified as PIP-dependent PCNA partners at stressed forks.

    Evidence Xenopus extract MMR reconstitution; single-molecule TIRF of PCNA–Rev1–polη complexes; co-IP/PIP-box mutant analysis for FANCM, TRAIP, HUWE1

    PMID:26825464 PMID:27146073 PMID:27325737 PMID:27402201 PMID:27462463

    Open questions at the time
    • Structural basis of MutSα-mediated unloading inhibition not determined
    • How PCNA coordinates multiple simultaneous partners in a physiological context remains unclear
  19. 2017 High

    The crystal structure of human PCNA on DNA revealed a right-hand spiral of basic residues inside the ring channel matching B-DNA pitch, defining a cogwheel sliding mechanism; mutations at this interface impaired Polδ-initiated DNA synthesis.

    Evidence X-ray crystallography, NMR, MD simulations, functional mutagenesis

    PMID:28071730

    Open questions at the time
    • How PCNA orientation on DNA influences partner recruitment directionality was not resolved
  20. 2019 High

    ATAD5-RLC was mechanistically defined as the principal PCNA unloader in human cells, acting through a single ATP-dependent intermediate distinct from the two-step RFC loading mechanism; PCNA was also shown to stimulate Polδ catalytic rate >10-fold beyond processivity, redefining its contribution to replication speed. Separately, surface-expressed PCNA was identified as an immune checkpoint ligand for NK receptor NKp44.

    Evidence In vitro loading/unloading with single-molecule resolution and ATPase mutants (ATAD5); quench-flow kinetics with PCNA mutants (Polδ stimulation); FACS binding/NK cytotoxicity/PDX mouse models (NKp44 ligand)

    PMID:30605530 PMID:31160570 PMID:31164357

    Open questions at the time
    • How ATAD5 activity is regulated at specific genomic loci is unknown
    • Physiological relevance of PCNA–NKp44 axis in human anti-tumor immunity requires clinical validation
  21. 2022 High

    Cryo-EM structures of the PCNA–FEN1–Lig1 toolbelt on nicked DNA provided the first atomic-resolution view of substrate handoff during Okazaki fragment maturation, showing sequential PIP-mediated recruitment of Lig1 to an unoccupied PCNA monomer after FEN1 cleavage.

    Evidence Cryo-EM structure determination, functional mutagenesis, biochemical ligation/binding assays

    PMID:36539424

    Open questions at the time
    • Whether additional enzymes (e.g., RNase H2) participate in an extended toolbelt is unknown
    • Dynamic transitions between toolbelt states in the cellular context have not been captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how PCNA coordinates the hierarchy of dozens of PIP/APIM-containing partners in real time during S phase; the structural basis of PCNA conformational changes upon DNA loading and modification; whether PCNA–NKp44 immune checkpoint signaling is therapeutically targetable; and the full genotype–phenotype spectrum of human PCNA mutations.
  • No in vivo real-time measurement of PCNA partner exchange hierarchy exists
  • No high-resolution structure of multiply modified (ubiquitinated + sumoylated) PCNA on DNA
  • Clinical significance of PCNA surface expression as immune ligand unconfirmed in patients

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0005198 structural molecule activity 3 GO:0003677 DNA binding 1 GO:0048018 receptor ligand activity 1
Localization
GO:0000228 nuclear chromosome 4 GO:0005654 nucleoplasm 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-73894 DNA Repair 16 R-HSA-392499 Metabolism of proteins 7 R-HSA-69306 DNA Replication 6 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2
Partners
ATAD5CDKN1AFEN1LIG1MSH6POLD1POLHRAD18
Complex memberships
PCNA homotrimerPCNA–FEN1–Lig1 toolbeltPCNA–Polδ replicative complexPCNA–RFC loading complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 p21 directly inhibits PCNA-dependent DNA replication by blocking PCNA's ability to activate DNA polymerase delta; this results from a direct protein-protein interaction between p21 and PCNA, demonstrated using SV40 DNA replication in vitro. In vitro SV40 DNA replication reconstitution assay; direct binding assay Nature High 7911228
1994 GADD45 (Gadd45) binds directly to PCNA, stimulates DNA excision repair in vitro, and inhibits entry of cells into S phase; the interaction is mediated by the N-terminal 94 amino acids of Gadd45 and maps to multiple regions of PCNA including its C-terminus. Co-immunoprecipitation, yeast two-hybrid, peptide ELISA, in vitro repair assay Science High 7784094 7973727
1996 Crystal structure of human PCNA complexed with a 22-residue C-terminal peptide of p21(WAF1/CIP1) at 2.6 Å resolution reveals p21 binds in a 1:1 stoichiometry per PCNA monomer via beta-sheet formation with the interdomain connector loop (IDCL), masking elements required for other polymerase assembly components while maintaining the intact trimeric ring. X-ray crystallography at 2.6 Å Cell High 8861913
1997 DNA-(cytosine-5) methyltransferase (DNMT1/MCMT) binds PCNA via a specific motif (amino acids 163–174 of MCMT); this interaction occurs at replication foci in intact cells and can be disrupted by a p21(WAF1) peptide, suggesting p21 regulates DNA methylation by blocking MCMT access to PCNA. Co-immunoprecipitation, cell imaging at replication foci, peptide competition assay Science High 9302295
1996 PCNA is required for DNA mismatch repair (MMR) at a step preceding DNA resynthesis; PCNA interacts with yeast MLH1 and MSH2 in two-hybrid assays; PCNA mutations elevate dinucleotide-repeat mutation rate epistatically with MLH1; p21 peptide inhibits MMR in human cell extracts and activity is restored by adding PCNA. Yeast two-hybrid, genetic epistasis, in vitro MMR assay with human cell extracts, p21 peptide inhibition Cell High 8858149
2002 PCNA is mono-ubiquitinated at K164 by RAD6/RAD18, modified by K63-linked poly-ubiquitination requiring MMS2/UBC13/RAD5, and sumoylated by UBC9—all at the same lysine residue. These modifications differentially affect DNA damage resistance and the RAD6-dependent post-replicative repair pathway; ubiquitination is conserved in yeast and humans. Biochemical modification assays, genetic epistasis in yeast, mass spectrometry, Western blot in yeast and human cells Nature High 12226657
2004 PCNA is monoubiquitinated at K164 following UV irradiation in human cells in an hRAD18-dependent manner; monoubiquitinated PCNA specifically interacts with DNA polymerase eta (poleta) via two motifs in poleta, providing a mechanism for the polymerase switch from replicative to translesion synthesis polymerase. Co-immunoprecipitation, Western blot, UV irradiation assays, domain mapping, interaction with purified proteins Molecular cell High 15149598
2004 RAD18/RAD6 monoubiquitinate PCNA in vitro; RAD18 guides poleta to replication-stalling sites through direct physical interaction with poleta and through PCNA monoubiquitination; poleta preferentially interacts with monoubiquitinated PCNA whereas polδ does not. In vitro ubiquitination assay with purified proteins, co-immunoprecipitation, UV-induced focus formation in RAD18-knockout cells, Western blot The EMBO journal High 15359278
2005 USP1 deubiquitinates monoubiquitinated PCNA, acting as a safeguard against error-prone translesion synthesis. UV irradiation triggers USP1 autocleavage at a diglycine motif, inactivating the DUB and allowing monoubiquitinated PCNA to accumulate and activate TLS. In vitro DUB assay, UV irradiation Western blot, autocleavage mapping, RNAi knockdown Nature cell biology High 16531995
2005 Y-family TLS polymerases (poleta, poliota) contain ubiquitin-binding domains (UBM and UBZ) required for binding ubiquitin, accumulation in replication factories, and interaction with monoubiquitinated PCNA. The UBZ domain of poleta is essential for restoring normal UV response in XP-V cells. Domain identification and mutagenesis, binding assays, cellular focus formation, complementation of XP-V cells Science High 16357261
2000 FEN1 interacts with PCNA through two distinct modes: in solution, FEN1 interacts mainly through the PCNA interdomain connector loop (IDCL); when PCNA encircles DNA, the C-terminal domain of PCNA is required for productive FEN1 stimulation. An FF→GA mutation in FEN1's PCNA-interaction domain abrogates both modes and causes replication and repair defects in vivo. Yeast PCNA mutant analysis, in vitro activity assays, DNA-coupled PCNA retention assay, in vivo phenotypic analysis The EMBO journal High 10899134
2001 PCNA binds to hMutSα (via hMSH6 subunit) and hMutSβ (via hMSH3 subunit) through a conserved PIP-box motif Qxx[LI]xx[FF] in the N-terminal domains. A deletion variant of hMutSα lacking this motif fails to interact with PCNA in vitro and cannot restore MMR in hMSH6-deficient cells. hMSH6 and hMSH3 colocalize with PCNA at replication foci. In vitro binding assay, co-localization by immunofluorescence, MMR complementation assay Genes & development High 11274057
2003 PCNA in the archaeon Sulfolobus solfataricus is a heterotrimer of three distinct subunits (PCNA1, 2, 3) that assembles in a defined order. The heterotrimer (but not individual subunits) stimulates DNA polymerase, DNA ligase I, and FEN1, with distinct subunits contacting each enzyme, imposing defined architecture at the lagging strand fork. Biochemical reconstitution, activity stimulation assays, protein interaction mapping Molecular cell High 12535540
2004 XRCC1 co-localizes with PCNA at DNA replication foci in S phase and physically interacts with PCNA both in vivo and in vitro; the interaction is direct and mediated by XRCC1 residues 166–310. This suggests PCNA sequesters XRCC1 to replication factories to facilitate single-strand break repair in S phase. Co-immunoprecipitation, FRET analysis, in vitro binding assay, immunofluorescence co-localization Nucleic acids research High 15107487
2005 The Ctf18-RFC complex (containing Ctf18, Dcc1, Ctf8, and small RFC subunits) efficiently unloads PCNA from DNA in an ATP hydrolysis-dependent manner. When single-stranded DNA is coated by RPA, Ctf18-RFC unloading activity predominates over loading. Neither RFC itself nor Rad24- or Elg1-containing complexes catalyze significant PCNA unloading. In vitro PCNA loading/unloading assay with purified yeast proteins, ATP hydrolysis requirement testing, RPA specificity assay Molecular and cellular biology High 15964801
2005 PCNA dynamics at replication foci and DNA damage sites differ: GFP-PCNA shows a dynamic equilibrium at replication foci, but a longer residence time at UV-damaged regions. Initial PCNA recruitment to damaged sites is dependent on nucleotide excision repair (NER). A ubiquitination-defective PCNA mutant (K164R) shows significantly shorter residence time at damaged areas, linking PCNA ubiquitination to its retention at damage sites for translesion synthesis. FRAP (fluorescence recovery after photobleaching), live-cell imaging with GFP-PCNA, UV laser damage, NER-mutant cell lines, ubiquitination mutant analysis Molecular and cellular biology High 16227586
2006 PCNA is phosphorylated on Tyr211 by nuclear EGFR, which stabilizes chromatin-bound PCNA protein and maintains its replication functions on chromatin. EGFR tyrosine kinase activity is required for this modification. In vivo phosphorylation assay, chromatin fractionation, EGFR kinase-dead mutants, co-immunoprecipitation, mass spectrometry Nature cell biology High 17115032
2006 DNA polymerase zeta (Polzeta)-dependent spontaneous mutagenesis in replication mutants requires ubiquitination and sumoylation of K164 of PCNA. A PCNA mutant defective for functional interactions with Polzeta (but not monoubiquitination by Rad6/Rad18) reveals a separate role for PCNA in regulating Polzeta mutagenic activity beyond K164 modification. Genetic epistasis in yeast, PCNA mutant analysis, mutagenesis assays The EMBO journal High 16957771
2006 PCNA ubiquitination at K164 is required for immunoglobulin hypermutation in vertebrates: PCNA(K164R) mutation in DT40 B cells strongly reduces AID-dependent single-nucleotide substitutions in the Ig light-chain locus, implicating the PCNA-ubiquitin pathway in recruiting error-prone polymerases for somatic hypermutation. PCNA K164R knock-in in DT40 cells, sequencing of Ig locus, RAD18-mutant analysis PLoS biology High 17105346
2008 SUMO modification of yeast PCNA at K164 is stimulated by DNA loading of PCNA: loading onto DNA is a prerequisite for sumoylation in vivo and greatly stimulates modification in vitro. DNA binding by the ligase Siz1 is not strictly required; the stimulatory effect of DNA is mainly attributable to DNA binding of PCNA itself, implying a conformational change upon loading. In vitro sumoylation assay, in vivo genetic analysis, S phase-specific modification assay The EMBO journal High 18701921
2008 Chk1 regulates DNA damage-induced PCNA ubiquitination by stabilizing Claspin, which in turn regulates RAD18 binding to chromatin. This function requires Claspin but not ATR; Timeless (a Claspin-associating protein) is also required for efficient PCNA ubiquitination. RNAi knockdown, Western blot for PCNA ubiquitination, chromatin fractionation, epistasis analysis Genes & development High 18451105
2009 hABH2 interacts with PCNA via a novel motif called APIM (AlkB homologue 2 PCNA-interacting motif), distinct from the canonical PIP box. APIM is present in >200 proteins involved in DNA maintenance, transcription, and cell cycle regulation; a cell-penetrating APIM peptide increases cellular sensitivity to cytostatic agents. Pull-down assays, co-localization at replication foci, APIM peptide functional assay, bioinformatic identification The Journal of cell biology High 19736315
2009 Defects in DNA ligase I (cdc9-1 mutant in yeast) trigger PCNA ubiquitylation at a novel site, Lys107, through a pathway requiring the E2 variant Mms2, E2 Ubc4, and E3 Rad5—distinct from the K164 ubiquitylation pathway (which uses Rad6/Rad18). PCNA K107R mutation renders DNA ligase I-deficient cells inviable. This modification is conserved in humans. Yeast genetics, Western blot with PCNA-K107R mutant, E2/E3 epistasis, human cell validation Nature cell biology High 20010813
2010 FEN1 is methylated at Arg192 (primarily) by an arginine methyltransferase; this methylation suppresses FEN1 phosphorylation at Ser187. Only the methylated (not phosphorylated) form of FEN1 strongly interacts with PCNA, ensuring correct timing of Okazaki fragment maturation. Mutations disrupting methylation cause unscheduled phosphorylation, failure to localize to replication/repair foci, defective Okazaki fragment maturation, and increased genomic mutations. Mass spectrometry, in vitro methylation/phosphorylation assays, PCNA interaction assays, immunofluorescence, cell cycle and mutation analysis Nature chemical biology High 20729856
2011 CRL4(Cdt2) E3 ubiquitin ligase degrades substrates (Cdt1, p21, Set8) by coupling proteolysis to substrate display on chromatin-bound PCNA via PIP degrons. This mechanism prevents rereplication in S phase. Biochemical reconstitution of substrate degradation, domain mapping, cell-based assays Genes & development High 21828267
2012 SETD8 methyltransferase methylates PCNA at K248; this modification stabilizes PCNA expression and significantly enhances the interaction between PCNA and FEN1. Loss of PCNA K248 methylation retards Okazaki fragment maturation, slows DNA replication, and increases DNA damage sensitivity. In vitro methylation assay, PCNA K248R/SETD8 knockdown, Okazaki fragment maturation assay, co-immunoprecipitation, Western blot Cancer research High 22556262
2012 The Srs2 C-terminal domain contains tandem receptor motifs—one binding PCNA and one binding SUMO—both of which are required to specifically recognize SUMO-modified PCNA. This structural mechanism explains how Srs2 is recruited specifically to SUMO-PCNA at replication forks to inhibit homologous recombination. Crystal structure, NMR, biochemical binding assays, functional analysis in yeast Nature High 22382979
2013 PCNA promotes processive DNA end resection by Exo1: after DNA damage, PCNA loads onto double-strand breaks and directly interacts with Exo1, tethering it to the DNA substrate and conferring processivity to Exo1 resection in a mechanism analogous to its role in DNA replication. Mammalian cell experiments, Xenopus nuclear extracts, purified protein in vitro assays, co-immunoprecipitation Nucleic acids research High 23939618
2014 CBP (and less efficiently p300) acetylate PCNA at Lys13, 14, 77, and 80, promoting removal of chromatin-bound PCNA and its proteasomal degradation after nucleotide excision repair (NER). Mutation of these lysines impairs DNA replication and repair, enhances UV sensitivity, and prevents PCNA degradation after damage. In vitro acetylation assay, PCNA mutant cell lines, UV sensitivity assays, Western blot, proteasome inhibitor experiments Nucleic acids research High 24939902
2014 A hypomorphic missense mutation in human PCNA (p.Ser228Ile) causes a DNA repair disorder with features of neurodegeneration and photosensitivity. The mutation does not affect protein levels or DNA replication, but profoundly alters PCNA's interaction with FEN1 and DNA Ligase 1, and impairs UV survival and RNA synthesis recovery. Patient cell analysis, protein interaction assays, UV survival assays, RNA synthesis recovery assay The Journal of clinical investigation High 24911150
2014 SIVA1 constitutively interacts with PCNA via a PIP motif and serves as a molecular bridge recruiting RAD18 to PCNA. SIVA1 knockdown compromises RAD18-dependent PCNA monoubiquitination and poleta focus formation, increasing UV sensitivity. Affinity purification, co-immunoprecipitation, RNAi knockdown, UV sensitivity and focus formation assays The Journal of cell biology High 24958773
2015 Phosphorylation of PCNA at Tyr211 by EGFR inhibits DNA mismatch repair by altering PCNA's interaction with MutSα and MutSβ and interfering with PCNA-dependent activation of MutLα endonuclease; Y211-phosphorylated PCNA also induces nucleotide misincorporation during DNA synthesis. In vitro MMR assay, nucleotide incorporation assay, co-immunoprecipitation, phospho-PCNA mutants Proceedings of the National Academy of Sciences of the United States of America High 25825764
2016 MutSα inhibits PCNA unloading through its PCNA-interacting motif, thereby extending the post-replicative window permissive to strand-specific MMR. DNA-bound PCNA itself serves as the strand discrimination signal in the absence of strand discontinuities. Xenopus egg extract reconstitution, PCNA unloading assay, MMR assay, PIP-box mutant MutSα eLife High 27402201
2016 HUWE1 (HECT ubiquitin ligase) interacts with PCNA at stalled replication forks and is essential for genomic stability by promoting replication of damaged DNA. HUWE1-knockout cells exhibit replication defects and DNA breakage, and HUWE1 mono-ubiquitinates H2AX to promote signaling at stalled forks. Co-immunoprecipitation, HUWE1 knockout cells, replication fork assays, H2AX ubiquitination assay EMBO reports High 27146073
2016 FANCM interacts with PCNA via a conserved PIP-box; this interaction is stimulated by replication stress. A FANCM PIP-box mutant is defective in promoting replication traverse of interstrand crosslinks and in facilitating FANCD2 monoubiquitination. Co-immunoprecipitation, PIP-box mutant analysis, replication traverse assay, FANCD2 ubiquitination assay Nucleic acids research High 26825464
2016 PCNA forms 'tool belt' complexes and 'Rev1 bridge' architectures during translesion synthesis, with PCNA simultaneously bound to two non-classical polymerases (Rev1 and polη). These complexes are dynamic and can interconvert architecture without dissociation. Single-molecule TIRF microscopy Nucleic acids research High 27325737
2016 SDE2 is cleaved at a diglycine motif via PCNA-interacting PIP-box and deubiquitinase activity; the cleaved SDE2 negatively regulates UV-induced PCNA monoubiquitination and counteracts replication stress. Cleaved SDE2 is degraded by CRL4CDT2 in a cell cycle- and damage-dependent manner; failure to degrade SDE2 impairs S phase progression. Mutant analysis, in vivo cleavage assay, PCNA interaction studies, ubiquitination assays, cell cycle analysis PLoS genetics High 27906959
2016 REV1 promotes PCNA monoubiquitylation after UV irradiation through enhanced interaction with ubiquitylated RAD18, facilitating release of non-ubiquitylated RAD18 and its recruitment to chromatin for TLS. Co-immunoprecipitation, Western blot, UV/HU/MMC/MMS treatment assays, RAD18 ubiquitylation analysis Journal of cell science Medium 26795561
2017 Crystal structure of human PCNA bound to DNA reveals a double patch of basic residues within the ring channel arranged in a right-hand spiral matching B-DNA pitch. PCNA slides via a 'cogwheel' mechanism with short-lived polar interactions maintaining invariant orientation on DNA. Mutation of PCNA-DNA interface residues impairs initiation of DNA synthesis by polymerase δ. X-ray crystallography, NMR, molecular dynamics simulations, functional mutagenesis Nature communications High 28071730
2018 PCNA unloading by Elg1 (yeast ATAD5 homolog) is required to coordinate replication-coupled nucleosome assembly with DNA replication forks in order to maintain heterochromatic silencing of HML and HMR through S phase. Yeast genetic analysis, silencing assays, Elg1 mutant phenotype analysis Proceedings of the National Academy of Sciences of the United States of America High 29440488
2019 ATAD5-RLC (the human RFC-like complex) possesses potent PCNA unloading activity; ATPase motif and collar domain of ATAD5 are crucial. ATAD5-RLC can unload ubiquitinated PCNA and does so through a single intermediate state before ATP hydrolysis, whereas RFC loads PCNA through two intermediate states separated by ATP hydrolysis. FEN1 can inhibit PCNA unloading by the yeast ATAD5 homolog Elg1. In vitro PCNA loading/unloading assays, single-molecule measurements, ATPase mutant analysis Nature communications High 31160570
2019 PCNA stimulates the catalytic (nucleotide incorporation) rate of DNA polymerase delta by >10-fold, beyond its role as a processivity factor. A yeast PCNA mutant (DD41,42AA) shows substantially less stimulation of Pol δ nucleotide incorporation rate, identifying the relevant PCNA face. Quench-flow kinetic measurements, EMSA, fluorescence anisotropy, PCNA mutant analysis Nucleic acids research High 30605530
2019 PCNA expressed on the surface of tumor cells acts as an inhibitory ligand for the NK cell receptor NKp44-isoform1, representing an innate immune checkpoint. An anti-PCNA mAb (14-25-9) blocks this interaction, increases NK cell IFNγ release and cytotoxic activity, and inhibits tumor growth in PDX mouse models. FACS-based receptor-ligand binding assay, NK cytotoxicity assay, ELISA, in vivo PDX mouse model Cancer immunology research High 31164357
2022 Cryo-EM structures show human DNA Ligase 1 (Lig1) recruits PCNA to nicked DNA using two PIP motifs (PIPN-term and PIPDBD). After assembly as two-stack rings around DNA, PIPN-term is released and only PIPDBD is required for ligation. PCNA forms a toolbelt with FEN1 on nicked DNA, recruiting Lig1 to an unoccupied PCNA monomer to drive the FEN1-to-Lig1 substrate handoff during Okazaki fragment maturation. Cryo-EM structure determination, functional mutagenesis, biochemical ligation and binding assays Nature communications High 36539424
2005 Two PCNA homotrimers can form a back-to-back doublet complex; Arg5 and Lys110 on the PCNA back face are contact points. A PCNA double trimer (but not a homotrimer alone) can simultaneously accommodate chromatin assembly factor-1 (CAF-1) and polymerase delta, suggesting this architecture couples chromatin remodeling with DNA replication. Cell extracts and purified protein doublet formation assay, mutation analysis, peptide inhibition, co-binding assay The Journal of biological chemistry Medium 15805117
2011 A FEN1 point mutation (F343A/F344A, FFAA) specifically abolishing the FEN1-PCNA interaction causes defects in RNA primer removal and long-patch BER, resulting in DNA breaks, Chk1 activation, and near-tetraploid aneuploidy. FFAA mutant mice develop aneuploidy-associated cancer at high frequency. Knock-in mouse model, biochemical repair assays, chromosomal analysis, Chk1 inhibitor rescue Cell research High 21383776
2016 TRAIP encodes a PCNA-interacting protein (via a PIP box) that migrates to stalled replication forks. Inactivation of TRAIP or its PCNA interaction compromises replication fork recovery and progression, and causes chromosome instability. Co-immunoprecipitation, PIP-box mutant analysis, replication fork assays, chromosome instability assay Cell discovery Medium 27462463

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 3482 8259215
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 1819 12226657
1994 The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1669 7911228
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
1994 Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science (New York, N.Y.) 938 7973727
2005 Nucleolar proteome dynamics. Nature 934 15635413
2003 Proliferating cell nuclear antigen (PCNA): a dancer with many partners. Journal of cell science 879 12829735
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature genetics 843 10888872
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
1997 Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science (New York, N.Y.) 756 9302295
1997 PCNA: structure, functions and interactions. Oncogene 743 9038370
2004 Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Molecular cell 733 15149598
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1996 Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. Cell 696 8861913
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science (New York, N.Y.) 596 16357261
2006 Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature 585 16964240
1993 Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes & development 569 8101826
2012 RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell 542 22980979
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1998 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Molecular cell 500 9774970
2006 Regulation of monoubiquitinated PCNA by DUB autocleavage. Nature cell biology 491 16531995
1996 Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell 490 8858149
2004 Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. The EMBO journal 479 15359278
2000 The puzzle of PCNA's many partners. BioEssays : news and reviews in molecular, cellular and developmental biology 376 11056476
2005 Nuclear dynamics of PCNA in DNA replication and repair. Molecular and cellular biology 343 16227586
2013 Regulation of PCNA-protein interactions for genome stability. Nature reviews. Molecular cell biology 310 23594953
2001 Proliferating cell nuclear antigen (PCNA): ringmaster of the genome. International journal of radiation biology 278 11682006
2004 The PCNA-RFC families of DNA clamps and clamp loaders. Progress in nucleic acid research and molecular biology 270 15210332
2017 Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork. Molecular cell 259 28157503
2006 Tyrosine phosphorylation controls PCNA function through protein stability. Nature cell biology 254 17115032
2014 PCNA: a silent housekeeper or a potential therapeutic target? Trends in pharmacological sciences 238 24655521
2016 The Many Roles of PCNA in Eukaryotic DNA Replication. The Enzymes 231 27241932
2020 Human PCNA Structure, Function and Interactions. Biomolecules 224 32276417
2001 hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci. Genes & development 195 11274057
2011 Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase. Genes & development 193 21828267
2003 A heterotrimeric PCNA in the hyperthermophilic archaeon Sulfolobus solfataricus. Molecular cell 182 12535540
2012 Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression. Cancer research 170 22556262
2004 XRCC1 co-localizes and physically interacts with PCNA. Nucleic acids research 162 15107487
1994 Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation. Gut 156 7909785
2009 Identification of a novel, widespread, and functionally important PCNA-binding motif. The Journal of cell biology 147 19736315
2006 A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS biology 138 17105346
2000 Two modes of FEN1 binding to PCNA regulated by DNA. The EMBO journal 134 10899134
1998 Protein-PCNA interactions: a DNA-scanning mechanism? Trends in biochemical sciences 132 9697409
2020 Targeting Proliferating Cell Nuclear Antigen (PCNA) as an Effective Strategy to Inhibit Tumor Cell Proliferation. Current cancer drug targets 131 31951183
1999 PCNA binding proteins. Frontiers in bioscience : a journal and virtual library 125 10577396
2020 bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA). Proceedings of the National Academy of Sciences of the United States of America 124 32123106
2005 Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex. Molecular and cellular biology 116 15964801
2012 Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2. Nature 115 22382979
2010 Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nature chemical biology 114 20729856
1995 Characterisation of the interaction between PCNA and Gadd45. Oncogene 112 7784094
1986 Nuclear patterns of cyclin (PCNA) antigen distribution subdivide S-phase in cultured cells--some applications of PCNA antibodies. Leukemia research 107 2419706
2004 Ubiquitination of PCNA and the polymerase switch in human cells. Cell cycle (Georgetown, Tex.) 106 15280666
2008 Chk1 and Claspin potentiate PCNA ubiquitination. Genes & development 94 18451105
2014 CBP and p300 acetylate PCNA to link its degradation with nucleotide excision repair synthesis. Nucleic acids research 85 24939902
2006 A novel function of DNA polymerase zeta regulated by PCNA. The EMBO journal 85 16957771
2019 Regulation of PCNA cycling on replicating DNA by RFC and RFC-like complexes. Nature communications 84 31160570
2011 Targeting tyrosine phosphorylation of PCNA inhibits prostate cancer growth. Molecular cancer therapeutics 79 21220489
2008 SUMO modification of PCNA is controlled by DNA. The EMBO journal 79 18701921
2017 Structural basis of human PCNA sliding on DNA. Nature communications 71 28071730
2014 Hypomorphic PCNA mutation underlies a human DNA repair disorder. The Journal of clinical investigation 69 24911150
2013 PCNA promotes processive DNA end resection by Exo1. Nucleic acids research 69 23939618
2008 The p21 and PCNA partnership: a new twist for an old plot. Cell cycle (Georgetown, Tex.) 69 19066467
2018 Maneuvers on PCNA Rings during DNA Replication and Repair. Genes 67 30126151
1989 Calf thymus DNA polymerase delta independent of proliferating cell nuclear antigen (PCNA). Nucleic acids research 62 2564661
2009 Defects in DNA ligase I trigger PCNA ubiquitylation at Lys 107. Nature cell biology 60 20010813
2015 Phosphorylation of PCNA by EGFR inhibits mismatch repair and promotes misincorporation during DNA synthesis. Proceedings of the National Academy of Sciences of the United States of America 59 25825764
2013 Targeting the EGFR/PCNA signaling suppresses tumor growth of triple-negative breast cancer cells with cell-penetrating PCNA peptides. PloS one 59 23593472
1999 Cyclin D1 inhibits cell proliferation through binding to PCNA and cdk2. Experimental cell research 59 9925749
1994 Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy. Digestive diseases and sciences 59 7906221
2012 CRL4(CDT2) targets CHK1 for PCNA-independent destruction. Molecular and cellular biology 58 23109433
2005 Proliferating cell nuclear antigen (PCNA) as a proliferative marker during embryonic and adult zebrafish hematopoiesis. Histochemistry and cell biology 58 16028068
2002 Cdc25C interacts with PCNA at G2/M transition. Oncogene 54 11896603
2015 PCNA-interacting peptides reduce Akt phosphorylation and TLR-mediated cytokine secretion suggesting a role of PCNA in cellular signaling. Cellular signalling 53 25797046
2006 Structure of the heterotrimeric PCNA from Sulfolobus solfataricus. Acta crystallographica. Section F, Structural biology and crystallization communications 53 17012780
2005 Sumoylation of PCNA: Wrestling with recombination at stalled replication forks. DNA repair 52 16368276
1999 Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) in malignant and nonmalignant skin diseases. Archives of dermatological research 51 10482011
2016 HUWE1 interacts with PCNA to alleviate replication stress. EMBO reports 50 27146073
2013 Readers of PCNA modifications. Chromosoma 50 23580141
2011 Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer. Cell research 48 21383776
2016 PCNA tool belts and polymerase bridges form during translesion synthesis. Nucleic acids research 47 27325737
2011 Dynamic regulation of PCNA ubiquitylation/deubiquitylation. FEBS letters 47 21640107
2005 Proliferating cell nuclear antigen (PCNA) may function as a double homotrimer complex in the mammalian cell. The Journal of biological chemistry 47 15805117
2016 FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks. Nucleic acids research 44 26825464
2004 Esophagin and proliferating cell nuclear antigen (PCNA) are biomarkers of human esophageal neoplastic progression. International journal of cancer 43 15221970
1994 p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa. European journal of cancer. Part B, Oral oncology 43 7719225
2006 Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in the pig ovary. Folia histochemica et cytobiologica 41 17219721
2002 On the road to repair: PCNA encounters SUMO and ubiquitin modifications. Molecular cell 41 12408814
2016 MutSα maintains the mismatch repair capability by inhibiting PCNA unloading. eLife 40 27402201
2012 The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA). Autoimmunity reviews 40 22381917
2018 Replisome Dynamics and Their Functional Relevance upon DNA Damage through the PCNA Interactome. Cell reports 39 30590055
2015 A proposal: Evolution of PCNA's role as a marker of newly replicated DNA. DNA repair 39 25704660
2012 Proliferative cell nuclear antigen (PCNA) expression in the intestine of Salmo trutta trutta naturally infected with an acanthocephalan. Parasites & vectors 39 22967751
2011 Ubiquitination of PCNA and its essential role in eukaryotic translesion synthesis. Cell biochemistry and biophysics 39 21461937
2006 Expression of survivin and correlation with PCNA in osteosarcoma. Journal of surgical oncology 39 16705726
2021 PCNA Loaders and Unloaders-One Ring That Rules Them All. Genes 38 34828416
2009 Ubiquitination and deubiquitination of PCNA in response to stalling of the replication fork. Cell cycle (Georgetown, Tex.) 38 19221475
2020 Control of DNA Damage Bypass by Ubiquitylation of PCNA. Genes 37 32013080
2014 SIVA1 directs the E3 ubiquitin ligase RAD18 for PCNA monoubiquitination. The Journal of cell biology 37 24958773
2019 PCNA accelerates the nucleotide incorporation rate by DNA polymerase δ. Nucleic acids research 36 30605530
2018 Pivotal roles of PCNA loading and unloading in heterochromatin function. Proceedings of the National Academy of Sciences of the United States of America 36 29440488
2016 TRAIP regulates replication fork recovery and progression via PCNA. Cell discovery 36 27462463
1986 Immunochemical and biochemical analysis of the proliferating cell nuclear antigen (PCNA) in HeLa cells. Experimental cell research 36 2869966
2011 The archaeal PCNA proteins. Biochemical Society transactions 35 21265741
2008 On the mechanism of loading the PCNA sliding clamp by RFC. Molecular microbiology 35 18312273
2019 Inhibition of the NKp44-PCNA Immune Checkpoint Using a mAb to PCNA. Cancer immunology research 34 31164357
2016 PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress. PLoS genetics 34 27906959
1992 PCNA expression in cutaneous keratinous neoplasms and verruca vulgaris. The American journal of pathology 34 1352943
1995 The significance of PCNA and p53 protein in some oral tumors. International journal of oral and maxillofacial surgery 33 7594756
2016 Dynamics of plant DNA replication based on PCNA visualization. Scientific reports 32 27417498
2001 Immunohistochemical study of p53, p21 and PCNA in pterygium. Acta histochemica 32 11368097
2020 DNA-damage tolerance through PCNA ubiquitination and sumoylation. The Biochemical journal 31 32726436
2006 Analysis of proliferating cell nuclear antigen (PCNA) associated with DNA. Methods in molecular biology (Clifton, N.J.) 30 16673899
1993 Proliferating cell nuclear antigen (PCNA): expression in samples of human astrocytic gliomas. Neuropathology and applied neurobiology 29 8100356
2022 Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing. Nature communications 27 36539424
1992 Proliferating cell nuclear antigen (PCNA) expression in Hodgkin's disease. The Journal of pathology 27 1360494
2016 REV1 promotes PCNA monoubiquitylation through interacting with ubiquitylated RAD18. Journal of cell science 26 26795561
1993 Expression of proliferating cell nuclear antigen (PCNA) in dysplasia of the bronchial epithelium. The Journal of pathology 26 8102179
2019 Spatiotemporal regulation of PCNA ubiquitination in damage tolerance pathways. Critical reviews in biochemistry and molecular biology 25 31736364
2011 9-1-1: PCNA's specialized cousin. Trends in biochemical sciences 25 21978893
1990 The promoter of the human proliferating cell nuclear antigen (PCNA) gene is bidirectional. Experimental cell research 25 1970785
1993 Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL). Leukemia & lymphoma 24 8106065