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User:Cboursnell/Sandbox/ORC6

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ORC6
Identifiers
SymbolORC6
PfamORC6
InterProIPR008721
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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


References

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  1. ^ Chesnokov IN (2007). "Multiple functions of the origin recognition complex". Int. Rev. Cytol. International Review of Cytology. 256: 69–109. doi:10.1016/S0074-7696(07)56003-1. ISBN 9780123737007. PMID 17241905.
  2. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  3. ^ 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.{{cite journal}}: CS1 maint: date and year (link)
  4. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  5. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  6. ^ 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.{{cite journal}}: CS1 maint: date and year (link)
  7. ^ 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. doi:10.1002/j.1460-2075.1995.tb07261.x. PMC 398377. PMID 7781615.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  8. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.{{cite journal}}: CS1 maint: date and year (link)
  12. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  13. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  14. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  15. ^ 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.{{cite journal}}: CS1 maint: date and year (link)
  16. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  17. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  18. ^ 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.{{cite journal}}: CS1 maint: date and year (link)
  19. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  20. ^ Randell JC, Bowers JL, Rodríguez 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  21. ^ 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.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  22. ^ 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.
  23. ^ Bell SP (March 2002). "The origin recognition complex: from simple origins to complex functions". Genes Dev. 16 (6): 659–72. doi:10.1101/gad.969602. PMID 11914271.{{cite journal}}: CS1 maint: date and year (link)
  24. ^ Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (October 2003). "Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859–64. doi:10.1038/nature02062. PMID 14574415.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  25. ^ Chen S, de Vries MA, Bell SP (November 2007). "Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading". Genes Dev. 21 (22): 2897–907. doi:10.1101/gad.1596807. PMC 2049192. PMID 18006685.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  26. ^ Wilmes GM, Archambault V, Austin RJ, Jacobson MD, Bell SP, Cross FR (May 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. doi:10.1101/gad.1202304. PMC 406289. PMID 15105375.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
This article incorporates text from the public domain Pfam and InterPro: IPR008721
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