PCNA
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PCNA
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| Sembol | ? |
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Proliferatif Hücre Çekirdek Antijeni, ya da sık kullanılan adıyla 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.
Konu başlıkları |
DNA sentezi sırasında çekirdekte gen ekspresyonu [değiştir]
PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle.[1] Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone.[2] PCNA helps hold DNA polymerase delta (Pol δ) to DNA. PCNA is clamped[3] to DNA through the action of replication factor C (RFC),[4] which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2F transcription factor-containing complexes.[5]
DNA Onarımındaki İşlevleri [değiştir]
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.[6]
PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair (PRR). In PRR, there are two sub-pathways: (1) translesion synthesis, which is carried out by specialised DNA polymerases that are able to incorporate damaged DNA bases into their active sites (unlike the normal replicative polymerase, which stall), and hence bypass the damage, and (2) a proposed "template switch" pathway that is thought to involve damage bypass by recruitment of the homologous recombination machinery. PCNA is pivotal to the activation of these pathways and the choice as to which pathway is utilised by the cell. PCNA becomes post-translationally modified by ubiquitin. Mono-ubiquitin of lysine number 164 on PCNA activates the translesion synthesis pathway. Extension of this mono-ubiquitin to form a non-canonical lysine-63-linked poly-ubiquitin chain is thought to activate the template switch pathway. Furthermore, sumoylation (by small ubiquitin-like modifier, SUMO) of PCNA lysine-164 (and to a lesser extent, lysine-127) inhibits the template switch pathway. This antagonistic effect occurs because sumoylated PCNA recruits a DNA helicase called Srs2, which has a role in disrupting Rad51 nucleoprotein filaments fundamental for initiation of homologous recombination. PRR is reviewed in Lehmann and Fuchs, 2006[7]
PCNA-bağlayan proteinler [değiştir]
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
detaylar için bakınız [8]
Ayrıca bakınız [değiştir]
- Transkripsiyon
- Ki-67 - hücre çoğalması belirteci
Dış bağlantılar [değiştir]
- MeSH PCNA
- "ANA: Cell cycle related (Mitotic): PCNA type 1 and type 2 Antibody Patterns". Antibody Patterns.com. http://www.antibodypatterns.com/mitotic.php. Erişim tarihi: 2008-04-15.
- Dan Krotz. "Structure of a Clamp–Loader Complex". Advanced Light Source News. http://www-als.lbl.gov/als/science/sci_archive/80slidingclamp.html. Erişim tarihi: 2008-04-15.[3]
- "Movie showing a model of clamp loading of PCNA onto DNA". http://www.pubmedcentral.gov/picrender.fcgi?artid=1236569&blobname=pnas_0506447102_06447Movie2.mov. Erişim tarihi: 2008-04-15.[9]
Kaynaklar [değiştir]
- ^ Leonardi E, Girlando S, Serio G, Mauri FA, Perrone G, Scampini S, Dalla Palma P, Barbareschi M (1992). "PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables". J. Clin. Pathol. 45 (5): 416–9. doi:10.1136/jcp.45.5.416. PMID 1350788.
- ^ Matsumoto K, Moriuchi T, Koji T, Nakane PK (1987). "Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin". EMBO J. 6 (3): 637–42. PMID 2884104. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=2884104.
- ^ a b Bowman GD, O'Donnell M, Kuriyan J (2004). "Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex". Nature 429 (6993): 724–30. doi:10.1038/nature02585. PMID 15201901.
- ^ Zhang G, Gibbs E, Kelman Z, O'Donnell M, Hurwitz J (1999). "Studies on the interactions between human replication factor C and human proliferating cell nuclear antigen". Proc. Natl. Acad. Sci. U.S.A. 96 (5): 1869–74. doi:10.1073/pnas.96.5.1869. PMID 10051561.
- ^ Egelkrout EM, Mariconti L, Settlage SB, Cella R, Robertson D, Hanley-Bowdoin L (2002). "Two E2F elements regulate the proliferating cell nuclear antigen promoter differently during leaf development". Plant Cell 14 (12): 3225–36. doi:10.1105/tpc.006403. PMID 12468739.
- ^ Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W (2005). "Nuclear dynamics of PCNA in DNA replication and repair". Mol. Cell. Biol. 25 (21): 9350–9. doi:10.1128/MCB.25.21.9350-9359.2005. PMID 16227586.
- ^ Lehmann AR (2006). "Gaps and forks in DNA replication: Rediscovering old models". DNA Repair (Amst). 5 (12): 1495-8. doi:10.1016/j.dnarep.2006.07.002. PMID 16956796.
- ^ Moldovan GL, Pfander B, Jentsch S (2007). "PCNA, the maestro of the replication fork". Cell 129 (4): 665–79. doi:10.1016/j.cell.2007.05.003. PMID 17512402.
- ^ Miyata T, Suzuki H, Oyama T, Mayanagi K, Ishino Y, Morikawa K (2005). "Open clamp structure in the clamp-loading complex visualized by electron microscopic image analysis". Proc. Natl. Acad. Sci. U.S.A. 102 (39): 13795–800. doi:10.1073/pnas.0506447102. PMID 16169902.
