PCNA

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.

PBB_Summary
section_title =
summary_text = 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.cite web | title = Entrez Gene: PCNA proliferating cell nuclear antigen| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5111| accessdate = ]

Expression in the nucleus during DNA synthesis

PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle.cite journal | author = Leonardi E, Girlando S, Serio G, Mauri FA, Perrone G, Scampini S, Dalla Palma P, Barbareschi M | title = PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables | journal = J. Clin. Pathol. | volume = 45 | issue = 5 | pages = 416–9 | year = 1992 | pmid = 1350788 | doi = 10.1136/jcp.45.5.416 | issn = ] Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone.cite journal | author = Matsumoto K, Moriuchi T, Koji T, Nakane PK | title = Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin | journal = EMBO J. | volume = 6 | issue = 3 | pages = 637–42 | year = 1987 | pmid = 2884104 | doi = | issn = | url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=2884104 ] PCNA helps hold DNA polymerase delta (Pol δ) to DNA. PCNA is clampedcite journal | author = Bowman GD, O'Donnell M, Kuriyan J | title = Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex | journal = Nature | volume = 429 | issue = 6993 | pages = 724–30 | year = 2004 | pmid = 15201901 | doi = 10.1038/nature02585 | | issn = ] to DNA through the action of replication factor C (RFC),cite journal | author = Zhang G, Gibbs E, Kelman Z, O'Donnell M, Hurwitz J | title = Studies on the interactions between human replication factor C and human proliferating cell nuclear antigen | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 5 | pages = 1869–74 | year = 1999 | pmid = 10051561 | doi = 10.1073/pnas.96.5.1869 | issn = ] which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2F transcription factor-containing complexes.cite journal | author = Egelkrout EM, Mariconti L, Settlage SB, Cella R, Robertson D, Hanley-Bowdoin L | title = Two E2F elements regulate the proliferating cell nuclear antigen promoter differently during leaf development | journal = Plant Cell | volume = 14 | issue = 12 | pages = 3225–36 | year = 2002 | pmid = 12468739 | doi = 10.1105/tpc.006403 | issn = ]

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.cite journal | author = Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W | title = Nuclear dynamics of PCNA in DNA replication and repair | journal = Mol. Cell. Biol. | volume = 25 | issue = 21 | pages = 9350–9 | year = 2005 | pmid = 16227586 | doi = 10.1128/MCB.25.21.9350-9359.2005 | issn = ] PCNA is also involved in the switch to DNA damage bypass translesion synthesis.

PCNA-binding proteins

DNA polymerases • Clamp loader • Flap endonuclease • DNA ligase • Topoisomerase • Replication licensing factor • E3 ubiquitin ligases • E2 SUMO-conjugating enzyme • Helicases, ATPases • Mismatch repair enzymes • Base excision repair enzymes • Nucleotide excision repair enzyme • Poly ADP ribose polymerase • Histone chaperone • Chromatin remodeling factor • Histone acetyltransferase • Histone deacetyltransferase • DNA methyltransferase • Sister-chromatid cohesion factors • Protein kinases • Cell-cycle regulators • Apoptotic factors

for details see cite journal |author=Moldovan GL, Pfander B, Jentsch S |title=PCNA, the maestro of the replication fork |journal=Cell |volume=129 |issue=4 |pages=665–79 |year=2007 |pmid=17512402 |doi=10.1016/j.cell.2007.05.003]

ee also

*Transcription
*Ki-67 - cellular marker for proliferation

External links

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*cite journal | author = Miyata T, Suzuki H, Oyama T, Mayanagi K, Ishino Y, Morikawa K | title = Open clamp structure in the clamp-loading complex visualized by electron microscopic image analysis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 102 | issue = 39 | pages = 13795–800 | year = 2005 | pmid = 16169902 | doi = 10.1073/pnas.0506447102 | issn = ]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Prosperi E |title=Multiple roles of the proliferating cell nuclear antigen: DNA replication, repair and cell cycle control. |journal=Progress in cell cycle research |volume=3 |issue= |pages= 193–210 |year= 1998 |pmid= 9552415 |doi=
*cite journal | author=Miura M |title=Detection of chromatin-bound PCNA in mammalian cells and its use to study DNA excision repair. |journal=J. Radiat. Res. |volume=40 |issue= 1 |pages= 1–12 |year= 1999 |pmid= 10408173 |doi=
*cite journal | author=Chen M, Pan ZQ, Hurwitz J |title=Sequence and expression in Escherichia coli of the 40-kDa subunit of activator 1 (replication factor C) of HeLa cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 7 |pages= 2516–20 |year= 1992 |pmid= 1313560 |doi=
*cite journal | author=Kemeny MM, Alava G, Oliver JM |title=Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2. |journal=J. Immunother. |volume=12 |issue= 4 |pages= 219–23 |year= 1993 |pmid= 1477073 |doi=
*cite journal | author=Morris GF, Mathews MB |title=Analysis of the proliferating cell nuclear antigen promoter and its response to adenovirus early region 1. |journal=J. Biol. Chem. |volume=265 |issue= 27 |pages= 16116–25 |year= 1990 |pmid= 1975809 |doi=
*cite journal | author=Webb G, Parsons P, Chenevix-Trench G |title=Localization of the gene for human proliferating nuclear antigen/cyclin by in situ hybridization. |journal=Hum. Genet. |volume=86 |issue= 1 |pages= 84–6 |year= 1991 |pmid= 1979311 |doi=
*cite journal | author=Travali S, Ku DH, Rizzo MG, "et al." |title=Structure of the human gene for the proliferating cell nuclear antigen. |journal=J. Biol. Chem. |volume=264 |issue= 13 |pages= 7466–72 |year= 1989 |pmid= 2565339 |doi=
*cite journal | author=Ku DH, Travali S, Calabretta B, "et al." |title=Human gene for proliferating cell nuclear antigen has pseudogenes and localizes to chromosome 20. |journal=Somat. Cell Mol. Genet. |volume=15 |issue= 4 |pages= 297–307 |year= 1989 |pmid= 2569765 |doi=
*cite journal | author=Prelich G, Kostura M, Marshak DR, "et al." |title=The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. |journal=Nature |volume=326 |issue= 6112 |pages= 471–5 |year= 1987 |pmid= 2882422 |doi= 10.1038/326471a0
*cite journal | author=Almendral JM, Huebsch D, Blundell PA, "et al." |title=Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 6 |pages= 1575–9 |year= 1987 |pmid= 2882507 |doi=
*cite journal | author=Chen IT, Smith ML, O'Connor PM, Fornace AJ |title=Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA. |journal=Oncogene |volume=11 |issue= 10 |pages= 1931–7 |year= 1995 |pmid= 7478510 |doi=
*cite journal | author=Li X, Li J, Harrington J, "et al." |title=Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen. |journal=J. Biol. Chem. |volume=270 |issue= 38 |pages= 22109–12 |year= 1995 |pmid= 7673186 |doi=
*cite journal | author=Fukuda K, Morioka H, Imajou S, "et al." |title=Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen. |journal=J. Biol. Chem. |volume=270 |issue= 38 |pages= 22527–34 |year= 1995 |pmid= 7673244 |doi=
*cite journal | author=Warbrick E, Lane DP, Glover DM, Cox LS |title=A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. |journal=Curr. Biol. |volume=5 |issue= 3 |pages= 275–82 |year= 1995 |pmid= 7780738 |doi=
*cite journal | author=Hall PA, Kearsey JM, Coates PJ, "et al." |title=Characterisation of the interaction between PCNA and Gadd45. |journal=Oncogene |volume=10 |issue= 12 |pages= 2427–33 |year= 1995 |pmid= 7784094 |doi=
*cite journal | author=Kato S, Sekine S, Oh SW, "et al." |title=Construction of a human full-length cDNA bank. |journal=Gene |volume=150 |issue= 2 |pages= 243–50 |year= 1995 |pmid= 7821789 |doi=
*cite journal | author=Matsuoka S, Yamaguchi M, Matsukage A |title=D-type cyclin-binding regions of proliferating cell nuclear antigen. |journal=J. Biol. Chem. |volume=269 |issue= 15 |pages= 11030–6 |year= 1994 |pmid= 7908906 |doi=
*cite journal | author=Szepesi A, Gelfand EW, Lucas JJ |title=Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T lymphocytes. |journal=Blood |volume=84 |issue= 10 |pages= 3413–21 |year= 1994 |pmid= 7949095 |doi=
*cite journal | author=Smith ML, Chen IT, Zhan Q, "et al." |title=Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. |journal=Science |volume=266 |issue= 5189 |pages= 1376–80 |year= 1994 |pmid= 7973727 |doi=
*cite journal | author=Pan ZQ, Chen M, Hurwitz J |title=The subunits of activator 1 (replication factor C) carry out multiple functions essential for proliferating-cell nuclear antigen-dependent DNA synthesis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 1 |pages= 6–10 |year= 1993 |pmid= 8093561 |doi=

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