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PCNA

The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]
Full Name
Proliferating Cell Nuclear Antigen
Function
Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. 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).
Biological Process
Base-excision repair, gap-fillingIEA:Ensembl
Cellular response to hydrogen peroxideIEA:Ensembl
Cellular response to UVManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to xenobiotic stimulusIEA:Ensembl
Epithelial cell differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Estrous cycleIEA:Ensembl
Heart developmentIEA:Ensembl
Leading strand elongationManual Assertion Based On ExperimentIBA:GO_Central
Liver regenerationIEA:Ensembl
Mismatch repairManual Assertion Based On ExperimentIDA:BHF-UCL
Mitotic telomere maintenance via semi-conservative replicationBy SimilarityISS:BHF-UCL
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Positive regulation of deoxyribonuclease activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of DNA repairManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of DNA-directed DNA polymerase activityManual Assertion Based On ExperimentIMP:UniProtKB
Replication fork processingBy SimilarityISS:BHF-UCL
Response to cadmium ionIEA:Ensembl
Response to dexamethasoneIEA:Ensembl
Response to estradiolIEA:Ensembl
Response to L-glutamateIEA:Ensembl
Translesion synthesisManual Assertion Based On ExperimentIDA:UniProtKB
Cellular Location
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.
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.
PTM
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:24939902, PubMed:19419956).
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:24939902, PubMed:20227374).
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 ARMT1/C6orf211.

Anti-PCNA antibodies

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Target: PCNA
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse, Rat, Rabbit
Clone: CF329
Application*: ELISA, WB, IHC, FC, IP
Target: PCNA
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CB214A
Application*: ELISA, WB, IHC
Target: PCNA
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CB327
Application*: WB, IHC
Target: PCNA
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: CBR075G
Application*: WB, IHC, ICC
Target: PCNA
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBAb182
Application*: WB, IH, IF
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: S1
Application*: WB, E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 3G8
Application*: WB, E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 3B1
Application*: WB, E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 3A9
Application*: WB, E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG3
Specificity: Human, S. pombe, S. frugiperda
Clone: PC8
Application*: IH, IP, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, S. pombe
Clone: PC11
Application*: IH, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Rat
Clone: CBYC-P221
Application*: E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human, Mouse, Rat, Pig, Chicken, Fruit fly, Yeast, Zebrafish
Clone: SPM350
Application*: WB, F, E, IC, IF, IP, P, C
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: PCNA/694
Application*: F, IF, P, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human, Insect, Yeast
Clone: PC5
Application*: WB, IH, P
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Chicken, Fruit fly, Mouse, Rat, Yeast
Clone: PC10
Application*: F, IC, C, P, IP, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG3
Specificity: Human
Clone: k1A3
Application*: WB, E
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse, Rat
Clone: IML-83
Application*: WB, P, C, IC
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 7H4F8
Application*: E, F, P, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human, Mouse, Monkey, Rat, Hamster
Clone: 6B12-D7-H9
Application*: WB, IP, IC
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Rat
Clone: 5A10
Application*: F, IC, IH, IPP, WB
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Yeast
Clone: 3G236
Application*: WB, IP, P, IC, IF
Target: PCNA
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: 3G1
Application*: IF, P
Target: PCNA
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: 339
Application*: WB, E, IC, IF
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 1G7
Application*: E, WB, P, IF, IC, IP
Target: PCNA
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: P60
Application*: E, WB, IH, IP
Target: PCNA
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: P56
Application*: E, WB, IH, IP
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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