Potential role of Cdc6 at the initiation of DNA replication.
In molecular biology,
origin recognition complex ( ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes.   ORC is a central component for  eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle. ORC directs DNA  replication throughout the genome and is required for its initiation.   ORC bound at replication origins serves as the foundation for assembly of the  pre-replication complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2- Mcm7 complex.   Pre-RC assembly during  G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase.    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.    
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).   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.   
Both Orc1 and Orc5 bind
ATP, though only Orc1 has ATPase activity. The  binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability. The ATPase activity of Orc1 is involved in formation of the pre-RC.    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. Interactions within ORC suggest that Orc2-3-6 may form a core complex.  
References [ edit ]
^ 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.
^ Origin Recognition Complex at the US National Library of Medicine Medical Subject Headings (MeSH)
^ 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.
^ 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.
^ a b c 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.
^ a b 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.
^ a b 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.
^ a b c 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.
^ 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.
^ 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.
^ a b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Triolo T, Sternglanz R (May 1996). "Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing". Nature. 381 (6579): 251–3. doi: 10.1038/381251a0. PMID 8622770.
^ Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J (June 1997). "The origin recognition complex, SIR1, and the S phase requirement for silencing". Science. 276 (5318): 1547–51. doi: 10.1126/science.276.5318.1547. PMID 9171055.
^ Klemm RD, Austin RJ, Bell SP (February 1997). "Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex". Cell. 88 (4): 493–502. doi: 10.1016/S0092-8674(00)81889-9. PMID 9038340.
^ Klemm RD, Bell SP (July 2001). "ATP bound to the origin recognition complex is important for preRC formation". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8361–7. doi: 10.1073/pnas.131006898. PMC 37444 . PMID 11459976.
^ Bowers JL, Randell JC, Chen S, Bell SP (December 2004). "ATP hydrolysis by ORC catalyzes reiterative Mcm2-7 assembly at a defined origin of replication". Mol. Cell. 16 (6): 967–78. doi: 10.1016/j.molcel.2004.11.038. PMID 15610739.
^ Randell JC, Bowers JL, Rodriguez HK, Bell SP (January 2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Mol. Cell. 21 (1): 29–39. doi: 10.1016/j.molcel.2005.11.023. PMID 16387651.
^ Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP (November 2006). "An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes". EMBO J. 25 (21): 5150–8. doi: 10.1038/sj.emboj.7601391. PMC 1630405 . PMID 17053779.
Further reading [ edit ]
This article incorporates text from the public domain Pfam and InterPro IPR007220
This article incorporates text from the public domain Pfam and InterPro IPR010748
This article incorporates text from the public domain Pfam and InterPro IPR008721