Proliferatini ćelijski nuklearni antigen

Proliferating cell nuclear antigen
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Proliferativni ćelijski nuklearni antigen (PCNA) je DNK stega koja deluje kao faktor procesivnosti za DNK polimerazu δ u eukariotskim ćelijama i koja je esencijalna za replikaciju. PCNA je homotrimer koji ostvaruje svoju procesivnost putem obuhvatanja DNK, pri čemu ona deluje kao osnova na kojoj se vezuju drugi proteini koji su neophodni za DNK replikaciju, DNK popravku, remodelovanje hromatina i epigenetiku.[1]

Mnogi proteini formiraju interakcije sa dva poznata PCNA-interagujuća motiva: PCNA interagujuća peptidna (PIP) kutija[2] i AlkB homolog 2 PCNA interagujući motiv (APIM).[3] Proteinsko vezivanje za PCNA putem PIP-kutije se uglavnom ostvaruje tokom DNK replikacije, dok su proteini koji se vezuju za PCNA putem APIM prvenstveno važni u kontekstu genotoksičnog stresa.[4]

U responsu na DNK oštećenje, ovaj protein biva ubikvitinisan i učestvuje u putu RAD6 zavisne DNK popravke. Poznate su dve transkriptne varijante koje kodiraju isti protein. Pseudogeni ovog gena su prisutni na hromozomu 4 i na X hromozomu.[5]

Interakcije

PCNA formira interakcije sa:

Proteini koji formiraju interakcije sa PCNA preko APIM obuhvataju ljudski AlkB homolog 2, TFIIS-L, TFII-I, Rad51B,[3] XPA,[69] ZRANB3,[70] i FBH1.[71]

Reference

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  • 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—2520. PMC 48692 Слободан приступ. PMID 1313560. doi:10.1073/pnas.89.7.2516. 
  • 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—223. PMID 1477073. doi:10.1097/00002371-199211000-00001. 
  • 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. doi:10.1007/bf00205180. 
  • Travali S, Ku DH, Rizzo MG, Ottavio L, Baserga R, Calabretta B (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, Huebner K, Baserga R (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. doi:10.1007/BF01534969. 
  • Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B (1987). „The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro”. Nature. 326 (6112): 471—5. PMID 2882422. doi:10.1038/326471a0. 
  • Almendral JM, Huebsch D, Blundell PA, Macdonald-Bravo H, Bravo R (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. PMC 304478 Слободан приступ. PMID 2882507. doi:10.1073/pnas.84.6.1575. 
  • 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”. Oncogene. 11 (10): 1931—7. PMID 7478510. 
  • Li X, Li J, Harrington J, Lieber MR, Burgers PM (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. doi:10.1074/jbc.270.38.22109. 
  • Fukuda K, Morioka H, Imajou S, Ikeda S, Ohtsuka E, Tsurimoto T (1995). „Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen”. J. Biol. Chem. 270 (38): 22527—34. PMID 7673244. doi:10.1074/jbc.270.38.22527. 
  • 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—282. PMID 7780738. doi:10.1016/S0960-9822(95)00058-3. 
  • Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS (1995). „Characterisation of the interaction between PCNA and Gadd45”. Oncogene. 10 (12): 2427—33. PMID 7784094. 
  • Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T (1995). „Construction of a human full-length cDNA bank”. Gene. 150 (2): 243—50. PMID 7821789. doi:10.1016/0378-1119(94)90433-2. 
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  • 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. PMC 45588 Слободан приступ. PMID 8093561. doi:10.1073/pnas.90.1.6. 

Spoljašnje veze

  • PCNA на US National Library of Medicine Medical Subject Headings (MeSH)
  • „ANA: Cell cycle related (Mitotic): PCNA type 1 and type 2 Antibody Patterns”. Antibody Patterns.com. Архивирано из оригинала 23. 09. 2015. г. Приступљено 2008-04-15. 
  • Dan Krotz. „Structure of a clamp–loader complex”. Advanced Light Source News. Lawrence Berkeley National Laboratory. Приступљено 2008-04-15. 
  • Bowman GD, O'Donnell M, Kuriyan J (2004). „Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex”. Nature. 429 (6993): 724—730. PMID 15201901. doi:10.1038/nature02585. 
  • „Movie showing a model of clamp loading of PCNA onto DNA”. Pubmed Central. [мртва веза]
  • 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—13800. PMC 1236569 Слободан приступ. PMID 16169902. doi:10.1073/pnas.0506447102. 
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PDB Galerija
  • 1axc​: Ljudski PCNA
    1axc​: Ljudski PCNA
  • 1u76​: Kristalna struktura hPCNA vezanog za ostatke 452-466 DNK polimeraze-delta, p66 podjedinice
    1u76​: Kristalna struktura hPCNA vezanog za ostatke 452-466 DNK polimeraze-delta, p66 podjedinice
  • 1u7b​: Kristalna struktura hPCNA vezanog za ostatke 331-350 flap endonukleaze-1 (FEN1)
    1u7b​: Kristalna struktura hPCNA vezanog za ostatke 331-350 flap endonukleaze-1 (FEN1)
  • 1ul1​: Kristalna struktura ljudskog FEN1-PCNA kompleksa
    1ul1​: Kristalna struktura ljudskog FEN1-PCNA kompleksa
  • 1vyj​: Strukturene i biohemijske studije ljudskog PCNA kompleksa pružaju bazu za asocijaciju sa CDK/CYCLIN
    1vyj​: Strukturene i biohemijske studije ljudskog PCNA kompleksa pružaju bazu za asocijaciju sa CDK/CYCLIN
  • 1vym​: Prirodna ljudska PCNA
    1vym​: Prirodna ljudska PCNA
  • 1w60​: Prirodna ljudska PCNA
    1w60​: Prirodna ljudska PCNA
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Separacija
i inicijacija
Prokariotska
(inicijacija)
Eukariotska
(priprema u
G1 fazi)
Oba
Replikacija
Prokariotska
(elongacija)
Eukariotska
(sinteza u
S fazi)
Oba
Kretanje: Procesivnost · DNK ligaza
Terminacija
B bsyn: dnk (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)