The assembled human DNA clamp, a trimer of the protein PCNA.
Available structures: 1axc, 1u76, 1u7b, 1ul1, 1vyj, 1vym, 1w60
Identifiers
Symbol(s)
PCNA; MGC8367
External IDs
OMIM: 176740MGI: 97503Homologene: 1945
Gene Ontology
Molecular Function:
• DNA binding • protein binding • DNA polymerase processivity factor activity • MutLalpha complex binding
Cellular Component:
• cyclin-dependent protein kinase holoenzyme complex • nucleus • nuclear lamina • DNA replication factor C complex • PCNA complex
Biological Process:
• regulation of progression through cell cycle • DNA replication • regulation of DNA replication • DNA repair • base-excision repair, gap-filling • intracellular protein transport • cell proliferation • phosphoinositide-mediated signaling
RNA expression pattern
More reference expression data
Orthologs
Human
Mouse
Entrez
5111
18538
Ensembl
ENSG00000132646
ENSMUSG00000027342
Uniprot
P12004
Q542J9
Refseq
NM_002592 (mRNA) NP_002583 (protein)
NM_011045 (mRNA) NP_035175 (protein)
Location
Chr 20: 5.04 - 5.06 Mb
Chr 2: 131.94 - 131.94 Mb
Pubmed search
[1]
[2]
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase delta in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome. It is an example of a DNA clamp.
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.[1]
PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle
[2]. Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone [3]. PCNA helps hold DNA polymerase delta (Pol δ) to DNA. PCNA is clamped [4] to DNA through the action of replication factor C (RFC) [5], which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2Ftranscription factor-containing complexes [6].
Role in DNA repair
Since DNA polymerase delta is involved in resynthesis of excised damaged DNA strands during DNA repair, PCNA is important for both DNA synthesis and DNA repair [7]. PCNA is also involved in the switch to DNA damage bypass translation synthesis.
^ E. Leonardi, S. Girlando, G. Serio, F. A. Mauri, G. Perrone, S. Scampini, P. Dalla Palma and M. Barbareschi (1992) "PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables" in Journal of Clinical Pathology. Volume 45, pages 416-419.Entrez PubMed 1350788
^ K. Matsumoto, T. Moriuchi, T. Koji and P. K. Nakane (1987) "Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin" in Journal of the European Molecular Biology Organization Volume 6, pages 637-642. Entrez PubMed 2884104
^ ab G. D. Bowman, M. O'Donnell and J. Kuriyan (2004) "Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex" in Nature Volume 429, pages 724-730. Entrez PubMed 15201901
^ G. Zhang, E. Gibbs, Z. Kelman, M. O'Donnell and J. Hurwitz (1999) "Studies on the interactions between human replication factor C and human proliferating cell nuclear antigen" in Proceedings of the National Academy of Sciences of the United States of America Volume 96, pages 1869-1874. Entrez PubMed 10051561
^ E. M. Egelkrout, I. Mariconti, S. B. Settlage, R. Cella, D. Robertson and L. Hanley-Bowdoin (2002) "Two E2F elements regulate the proliferating cell nuclear antigen promoter differently during leaf development" in The Plant Cell Volume 14, pages 3225-36. Entrez PubMed 12468739
^ J. Essers, A. F. Theil, C. Baldeyron, W. A. van Cappellen, A. B. Houtsmuller, R. Kanaar and W. Vermeulen (2005) "Nuclear dynamics of PCNA in DNA replication and repair" Molecular and Cellular Biology Volume 25, pages 9350-9359. Entrez PubMed 16227586
^ T.Miyata, H. Suzuki, T. Oyama, K. Mayanagi, Y.Ishino and K. Morikawa (2005) "Open clamp structure in the clamp-loading complex visualized by electron microscopic image analysis" in Proceedings of the National Academy of Sciences of the United States of America Volume 102, pages 13795-13800.Entrez PubMed 16169902
Further reading
Prosperi E (1998). "Multiple roles of the proliferating cell nuclear antigen: DNA replication, repair and cell cycle control.". Progress in cell cycle research3: 193-210. PMID 9552415.
Miura M (1999). "Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair.". J. Radiat. Res.40 (1): 1-12. PMID 10408173.
Chen M, Pan ZQ, Hurwitz J (1992). "Sequence and expression in Escherichia coli of the 40-kDa subunit of activator 1 (replication factor C) of HeLa cells.". Proc. Natl. Acad. Sci. U.S.A.89 (7): 2516-20. PMID 1313560.
Kemeny MM, Alava G, Oliver JM (1993). "Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2.". J. Immunother.12 (4): 219-23. PMID 1477073.
Morris GF, Mathews MB (1990). "Analysis of the proliferating cell nuclear antigen promoter and its response to adenovirus early region 1.". J. Biol. Chem.265 (27): 16116-25. PMID 1975809.
Webb G, Parsons P, Chenevix-Trench G (1991). "Localization of the gene for human proliferating nuclear antigen/cyclin by in situ hybridization.". Hum. Genet.86 (1): 84-6. PMID 1979311.
Travali S, Ku DH, Rizzo MG, et al. (1989). "Structure of the human gene for the proliferating cell nuclear antigen.". J. Biol. Chem.264 (13): 7466-72. PMID 2565339.
Ku DH, Travali S, Calabretta B, et al. (1989). "Human gene for proliferating cell nuclear antigen has pseudogenes and localizes to chromosome 20.". Somat. Cell Mol. Genet.15 (4): 297-307. PMID 2569765.
Prelich G, Kostura M, Marshak DR, et al. (1987). "The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro.". Nature326 (6112): 471-5. doi:10.1038/326471a0. PMID 2882422.
Almendral JM, Huebsch D, Blundell PA, et al. (1987). "Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins.". Proc. Natl. Acad. Sci. U.S.A.84 (6): 1575-9. PMID 2882507.
Chen IT, Smith ML, O'Connor PM, Fornace AJ (1995). "Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA.". Oncogene11 (10): 1931-7. PMID 7478510.
Li X, Li J, Harrington J, et al. (1995). "Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen.". J. Biol. Chem.270 (38): 22109-12. PMID 7673186.
Fukuda K, Morioka H, Imajou S, et al. (1995). "Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen.". J. Biol. Chem.270 (38): 22527-34. PMID 7673244.
Warbrick E, Lane DP, Glover DM, Cox LS (1995). "A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen.". Curr. Biol.5 (3): 275-82. PMID 7780738.
Hall PA, Kearsey JM, Coates PJ, et al. (1995). "Characterisation of the interaction between PCNA and Gadd45.". Oncogene10 (12): 2427-33. PMID 7784094.
Kato S, Sekine S, Oh SW, et al. (1995). "Construction of a human full-length cDNA bank.". Gene150 (2): 243-50. PMID 7821789.
Matsuoka S, Yamaguchi M, Matsukage A (1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen.". J. Biol. Chem.269 (15): 11030-6. PMID 7908906.
Szepesi A, Gelfand EW, Lucas JJ (1994). "Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T lymphocytes.". Blood84 (10): 3413-21. PMID 7949095.
Smith ML, Chen IT, Zhan Q, et al. (1994). "Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.". Science266 (5189): 1376-80. PMID 7973727.
Pan ZQ, Chen M, Hurwitz J (1993). "The subunits of activator 1 (replication factor C) carry out multiple functions essential for proliferating-cell nuclear antigen-dependent DNA synthesis.". Proc. Natl. Acad. Sci. U.S.A.90 (1): 6-10. PMID 8093561.
