Kompleks prepoznavanja mesta početka

U molekularnoj biologiji, ORC ili Kompleks prepoznavanja početka (engl. origin recognition complex) je multi-podjedinični DNK vezujući kompleks (6 podjedinica) koji se vezuje kod svih eukariota u ATP-zavisnom maniru za mesto početka replikacije. Podjedinice ovog kompleksa su kodirane ORC1, ORC2, ORC3, ORC4, ORC5 i ORC6 genima.[2][3][4] ORC je centralna komponenta za eukariotsku replikaciju DNK, i vezivanje hromatina na mestu početka replikacije tokom ćelijskog ciklusa.[5] ORC usmerava DNK replikaciju širom genoma i neophodan je za inicijaciju.[6][7][8] ORC koji je vezan za mesto početka replikacije služi kao fondacija za formiranje prereplikacionog kompleksa (pre-RC), koji obuhvata Cdc6, Tah11 (aka Cdt1), i Mcm2-Mcm7 kompleks.[9][10][11] Formiranje Pre-RC kompleksa tokom G1 je neophodno za replikaciono licenciranje hromozoma pre DNK sinteze tokom S faze.[12][13][14] Ćelijskim ciklusom regulisana fosforilacija Orc2, Orc6, Cdc6, i MCM posredstvom ciklin-zavisne proteinske kinaze Cdc28 reguliše inicijaciju DNK replikacije, uklučujući blokiranje reinicijacije u G2/M fazi.[5][15][16][17]

Kompleks prepoznavanja početka podjedinica 2
Identifikatori
Simbol ORC2
Pfam PF04084
InterPro IPR007220
Kompleks prepoznavanja početka (ORC) podjedinica 3 N-terminus
Identifikatori
Simbol ORC3_N
Pfam PF07034
InterPro IPR010748
Kompleks prepoznavanja početka podjedinica 6 (ORC6)
Identifikatori
Simbol ORC6
Pfam PF05460
InterPro IPR008721
Potencijalna uloga Cdc6 u inicijaciji DNK replikacije.[1]

Reference uredi

  1. Borlado LR, Méndez J (February 2008). „CDC6: from DNA replication to cell cycle checkpoints and oncogenesis”. Carcinogenesis 29 (2): 237–43. DOI:10.1093/carcin/bgm268. PMID 18048387. 
  2. MeSH Origin+Recognition+Complex
  3. Dutta A, Bell SP (1997). „Initiation of DNA replication in eukaryotic cells”. Annu. Rev. Cell Dev. Biol. 13: 293–332. DOI:10.1146/annurev.cellbio.13.1.293. PMID 9442876. 
  4. Chesnokov IN (2007). „Multiple functions of the origin recognition complex”. Int. Rev. Cytol. 256: 69–109. DOI:10.1016/S0074-7696(07)56003-1. PMID 17241905. 
  5. 5,0 5,1 Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T (December 2007). „Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins”. FEMS Yeast Res. 7 (8): 1263–9. DOI:10.1111/j.1567-1364.2007.00298.x. PMID 17825065. 
  6. Bell SP, Stillman B (May 1992). „ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex”. Nature 357 (6374): 128–34. DOI:10.1038/357128a0. PMID 1579162. 
  7. Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (November 1995). „The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing”. Cell 83 (4): 563–8. DOI:10.1016/0092-8674(95)90096-9. PMID 7585959. 
  8. Gibson DG, Bell SP, Aparicio OM (June 2006). „Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae”. Genes Cells 11 (6): 557–73. DOI:10.1111/j.1365-2443.2006.00967.x. PMID 16716188. 
  9. Rao H, Stillman B (March 1995). „The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators”. Proc. Natl. Acad. Sci. U.S.A. 92 (6): 2224–8. DOI:10.1073/pnas.92.6.2224. PMC 42456. PMID 7892251. 
  10. Rowley A, Cocker JH, Harwood J, Diffley JF (June 1995). „Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC”. EMBO J. 14 (11): 2631–41. PMC 398377. PMID 7781615. 
  11. Speck C, Chen Z, Li H, Stillman B (November 2005). „ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA”. Nat. Struct. Mol. Biol. 12 (11): 965–71. DOI:10.1038/nsmb1002. PMC 2952294. PMID 16228006. 
  12. Kelly TJ, Brown GW (2000). „Regulation of chromosome replication”. Annu. Rev. Biochem. 69: 829–80. DOI:10.1146/annurev.biochem.69.1.829. PMID 10966477. 
  13. Bell SP, Dutta A (2002). „DNA replication in eukaryotic cells”. Annu. Rev. Biochem. 71: 333–74. DOI:10.1146/annurev.biochem.71.110601.135425. PMID 12045100. 
  14. Stillman B (February 2005). „Origin recognition and the chromosome cycle”. FEBS Lett. 579 (4): 877–84. DOI:10.1016/j.febslet.2004.12.011. PMID 15680967. 
  15. Weinreich M, Liang C, Chen HH, Stillman B (September 2001). „Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle”. Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11211–7. DOI:10.1073/pnas.201387198. PMC 58709. PMID 11572976. 
  16. Nguyen VQ, Co C, Li JJ (June 2001). „Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms”. Nature 411 (6841): 1068–73. DOI:10.1038/35082600. PMID 11429609. 
  17. Archambault V, Ikui AE, Drapkin BJ, Cross FR (August 2005). „Disruption of mechanisms that prevent rereplication triggers a DNA damage response”. Mol. Cell. Biol. 25 (15): 6707–21. DOI:10.1128/MCB.25.15.6707-6721.2005. PMC 1190345. PMID 16024805. 

Literatura uredi