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Symbol ORC6
Pfam ORC6
InterPro IPR008721

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded in yeast by ORC1-6.[1] ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle.[2] ORC directs DNA replication throughout the genome and is required for its initiation.[3][4][5] ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex.[6][7][8] Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase.[9][10][11] Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase.[2][12][13][14]

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR).[3][4][5] ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers.[5][15][16]

Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity.[17] The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability.[8] The ATPase activity of Orc1 is involved in formation of the pre-RC.[18][19][20] ATP binding by Orc5 is crucial for the stability of ORC as a whole. Only the Orc1-5 subunits are required for origin binding; Orc6 is essential for maintenance of pre-RCs once formed.[21] Interactions within ORC suggest that Orc2-3-6 may form a core complex.[2]

ORC homologues have been found in various eukaryotes, including fission yeast, insects, amphibians, and humans.[22]

This entry represents subunit 6, which directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; interacts with Spp1 and with trimethylated histone H3; phosphorylated by Cdc28.[23][24]

In Saccharomyces cerevisiae (Baker's yeast), both ends of the Orc6 interact with Cdt1 [25] and the N terminus mediates an interaction with the S-phase cyclin Clb5.[26]

Category:Protein families


  1. ^ Chesnokov IN (2007). "Multiple functions of the origin recognition complex". Int. Rev. Cytol. 256: 69–109. PMID 17241905. doi:10.1016/S0074-7696(07)56003-1. 
  2. ^ a b c Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T (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. PMID 17825065. doi:10.1111/j.1567-1364.2007.00298.x.  Unknown parameter |month= ignored (help)
  3. ^ a b Bell SP, Stillman B (1992). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature. 357 (6374): 128–34. PMID 1579162. doi:10.1038/357128a0.  Unknown parameter |month= ignored (help)
  4. ^ a b Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B (1995). "The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing". Cell. 83 (4): 563–8. PMID 7585959.  Unknown parameter |month= ignored (help)
  5. ^ a b c Gibson DG, Bell SP, Aparicio OM (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. PMID 16716188. doi:10.1111/j.1365-2443.2006.00967.x.  Unknown parameter |month= ignored (help)
  6. ^ Rao H, Stillman B (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. PMC 42456Freely accessible. PMID 7892251.  Unknown parameter |month= ignored (help)
  7. ^ Rowley A, Cocker JH, Harwood J, Diffley JF (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 398377Freely accessible. PMID 7781615.  Unknown parameter |month= ignored (help)
  8. ^ a b Speck C, Chen Z, Li H, Stillman B (2005). "ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA". Nat. Struct. Mol. Biol. 12 (11): 965–71. PMC 2952294Freely accessible. PMID 16228006. doi:10.1038/nsmb1002.  Unknown parameter |month= ignored (help)
  9. ^ Kelly TJ, Brown GW (2000). "Regulation of chromosome replication". Annu. Rev. Biochem. 69: 829–80. PMID 10966477. doi:10.1146/annurev.biochem.69.1.829. 
  10. ^ Bell SP, Dutta A (2002). "DNA replication in eukaryotic cells". Annu. Rev. Biochem. 71: 333–74. PMID 12045100. doi:10.1146/annurev.biochem.71.110601.135425. 
  11. ^ Stillman B (2005). "Origin recognition and the chromosome cycle". FEBS Lett. 579 (4): 877–84. PMID 15680967. doi:10.1016/j.febslet.2004.12.011.  Unknown parameter |month= ignored (help)
  12. ^ Weinreich M, Liang C, Chen HH, Stillman B (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. PMC 58709Freely accessible. PMID 11572976. doi:10.1073/pnas.201387198.  Unknown parameter |month= ignored (help)
  13. ^ Nguyen VQ, Co C, Li JJ (2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. 411 (6841): 1068–73. PMID 11429609. doi:10.1038/35082600.  Unknown parameter |month= ignored (help)
  14. ^ Archambault V, Ikui AE, Drapkin BJ, Cross FR (2005). "Disruption of mechanisms that prevent rereplication triggers a DNA damage response". Mol. Cell. Biol. 25 (15): 6707–21. PMC 1190345Freely accessible. PMID 16024805. doi:10.1128/MCB.25.15.6707-6721.2005.  Unknown parameter |month= ignored (help)
  15. ^ Triolo T, Sternglanz R (1996). "Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing". Nature. 381 (6579): 251–3. PMID 8622770. doi:10.1038/381251a0.  Unknown parameter |month= ignored (help)
  16. ^ Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J (1997). "The origin recognition complex, SIR1, and the S phase requirement for silencing". Science. 276 (5318): 1547–51. PMID 9171055.  Unknown parameter |month= ignored (help)
  17. ^ Klemm RD, Austin RJ, Bell SP (1997). "Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex". Cell. 88 (4): 493–502. PMID 9038340.  Unknown parameter |month= ignored (help)
  18. ^ Klemm RD, Bell SP (2001). "ATP bound to the origin recognition complex is important for preRC formation". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8361–7. PMC 37444Freely accessible. PMID 11459976. doi:10.1073/pnas.131006898.  Unknown parameter |month= ignored (help)
  19. ^ Bowers JL, Randell JC, Chen S, Bell SP (2004). "ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication". Mol. Cell. 16 (6): 967–78. PMID 15610739. doi:10.1016/j.molcel.2004.11.038.  Unknown parameter |month= ignored (help)
  20. ^ Randell JC, Bowers JL, Rodríguez HK, Bell SP (2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Mol. Cell. 21 (1): 29–39. PMID 16387651. doi:10.1016/j.molcel.2005.11.023.  Unknown parameter |month= ignored (help)
  21. ^ Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP (2006). "An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes". EMBO J. 25 (21): 5150–8. PMC 1630405Freely accessible. PMID 17053779. doi:10.1038/sj.emboj.7601391.  Unknown parameter |month= ignored (help)
  22. ^ Dutta A, Bell SP (1997). "Initiation of DNA replication in eukaryotic cells". Annu. Rev. Cell Dev. Biol. 13: 293–332. PMID 9442876. doi:10.1146/annurev.cellbio.13.1.293. 
  23. ^ Bell SP (2002). "The origin recognition complex: from simple origins to complex functions". Genes Dev. 16 (6): 659–72. PMID 11914271. doi:10.1101/gad.969602.  Unknown parameter |month= ignored (help)
  24. ^ Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (2003). "Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859–64. PMID 14574415. doi:10.1038/nature02062.  Unknown parameter |month= ignored (help)
  25. ^ Chen S, de Vries MA, Bell SP (2007). "Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading". Genes Dev. 21 (22): 2897–907. PMC 2049192Freely accessible. PMID 18006685. doi:10.1101/gad.1596807.  Unknown parameter |month= ignored (help)
  26. ^ Wilmes GM, Archambault V, Austin RJ, Jacobson MD, Bell SP, Cross FR (2004). "Interaction of the S-phase cyclin Clb5 with an "RXL" docking sequence in the initiator protein Orc6 provides an origin-localized replication control switch". Genes Dev. 18 (9): 981–91. PMC 406289Freely accessible. PMID 15105375. doi:10.1101/gad.1202304.  Unknown parameter |month= ignored (help)

This article incorporates text from the public domain Pfam and InterPro IPR008721