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proliferating cell nuclear antigen (PCNA)

Function: - component of multiple Cdk complexes in normal cells - binding of PCNA to GADD45 may displace PCNA from Cdk complexes - functions as a processivity factor for DNA polymerase delta & DNA polymerase epsilon - required for both DNA replication & DNA excision repair [5] - stoichiometrically inhibited by p53-induced p21WAF1/CIP1 - associated with viral & cellular replication origins [3] - binds to DNA only in presence of DNA polymerase gamma &/or replication factor C (RF-C) - stimulates activity of DNA polymerase delta & DNA polymerase epsilon {repair polymerases} by enabling turnover of polymerase (release of polymerase from template) - required for nucleotide excision repair in vitro [3] - RF-C, PCNA & DNA plymerase epsilon may act coordinately in DNA excision repair synthesis [4] Structure: - seems to exist in multiple forms Compartment: - present in nuclei in excess of GADD45 - nuclear redistribution of PCNA occurs subsequent to genotoxic insult, from sites of DNA replication to sites of DNA repair (putative)

Interactions

molecular events

Related

cyclin-dependent kinase inhibitor 1; p21WAF1/CIP1; p21; CDK-interacting protein 1; melanoma differentiation-associated protein 6; MDA-6 (CDKN1A, CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1) DNA polymerase delta DNA polymerase epsilon growth arrest & DNA-damage inducible-45 (GADD45) PCNA-associated factor; hepatitis C virus NS5A-transactivated protein 9; HCV NS5A-transactivated protein 9; overexpressed in anaplastic thyroid carcinoma 1; OEATC-1; p15PAF (KIAA0101, NS5ATP9, PAF, L5) replication factor-C

General

DNA-binding protein

Properties

SIZE: MW = 36-37 kD COMPARTMENT: cell nucleus MOTIF: DNA-binding motif SITE: 61-80 binding site FOR-BINDING-OF: growth arrest & DNA-damage inducible-45 (GADD45) binding site FOR-BINDING-OF: cyclin-dependent kinase inhibitor 1

References

  1. Linn S How many pols does it take to replicate nuclear DNA? Cell 66:185 1991 PMID: 1855251
  2. Nichols AF, Sancar A. Purification of PCNA as a nucleotide excision repair protein. Nucleic Acids Res. 1992 Jul 11;20(13):2441-6. PMID: 1352873
  3. Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 1994 Nov 25;266(5189):1376-80. PMID: 7973727
  4. Lehmann AR. Nucleotide excision repair and the link with transcription. Trends Biochem Sci. 1995 Oct;20(10):402-5. Review. PMID: 8533152
  5. Pan ZQ, Reardon JT, Li L, Flores-Rozas H, Legerski R, Sancar A, Hurwitz J. Inhibition of nucleotide excision repair by the cyclin- dependent kinase inhibitor p21. J Biol Chem. 1995 Sep 15;270(37):22008-16. PMID: 7665622
  6. Entrez Gene :accession 5111

Component-of

molecular complex

Databases & Figures

OMIM 176740 UniProt P12004 Entrez Gene 5111 Figures/diagrams/slides/tables related to proliferating cell nuclear antigen