In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea 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.[1][2][3] ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle.[4]
ORC directs DNA replication throughout the genome and is required for its initiation.[5][6][7] ORC and Noc3p bound at replication origins serve as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (a.k.a. Cdt1), and the Mcm2-Mcm7 complex.[8][9][10][11] Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase.[12][13][14] 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.[4][15][16][17]
The ORC is present throughout the cell cycle bound to replication origins, but is only active in late mitosis and early G1.
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).[5][6][7] 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.[7][18][19]
Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity.[20] The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability.[11] The ATPase activity of Orc1 is involved in formation of the pre-RC.[21][22][23] 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.[24] Interactions within ORC suggest that Orc2-3-6 may form a core complex.[4] A 2020 report suggests that budding yeast ORC dimerizes in a cell cycle dependent manner to control licensing.[25][26]
^Origin+Recognition+Complex at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
^Dutta A, Bell SP (1997). "Initiation of DNA replication in eukaryotic cells". Annual Review of Cell and Developmental Biology. 13: 293–332. doi:10.1146/annurev.cellbio.13.1.293. PMID 9442876.
^Chesnokov IN (2007). Multiple functions of the origin recognition complex. International Review of Cytology. Vol. 256. pp. 69–109. doi:10.1016/S0074-7696(07)56003-1. ISBN 9780123737007. PMID 17241905.
^ abcMatsuda 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 Research. 7 (8): 1263–9. doi:10.1111/j.1567-1364.2007.00298.x. PMID 17825065.
^ abBell SP, Stillman B (May 1992). "ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex". Nature. 357 (6374): 128–34. Bibcode:1992Natur.357..128B. doi:10.1038/357128a0. PMID 1579162. S2CID 4346767.
^ abBell 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.
^ abcGibson 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 to Cells. 11 (6): 557–73. doi:10.1111/j.1365-2443.2006.00967.x. PMID 16716188. S2CID 22439595.
^Zhang Y, Yu Z, Fu X, Liang C (June 2002). "Noc3p, a bHLH Protein, Plays an Integral Role in the Initiation of DNA Replication in Budding Yeast". Cell. 109 (7): 849–860. doi:10.1016/s0092-8674(02)00805-x. PMID 12110182.
^Rao H, Stillman B (March 1995). "The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators". Proceedings of the National Academy of Sciences of the United States of America. 92 (6): 2224–8. Bibcode:1995PNAS...92.2224R. 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". The EMBO Journal. 14 (11): 2631–41. doi:10.1002/j.1460-2075.1995.tb07261.x. PMC 398377. PMID 7781615.
^ abSpeck C, Chen Z, Li H, Stillman B (November 2005). "ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA". Nature Structural & Molecular Biology. 12 (11): 965–71. doi:10.1038/nsmb1002. PMC 2952294. PMID 16228006.
^Kelly TJ, Brown GW (2000). "Regulation of chromosome replication". Annual Review of Biochemistry. 69: 829–80. doi:10.1146/annurev.biochem.69.1.829. PMID 10966477.
^Bell SP, Dutta A (2002). "DNA replication in eukaryotic cells". Annual Review of Biochemistry. 71: 333–74. doi:10.1146/annurev.biochem.71.110601.135425. PMID 12045100.
^Stillman B (February 2005). "Origin recognition and the chromosome cycle". FEBS Letters. 579 (4): 877–84. doi:10.1016/j.febslet.2004.12.011. PMID 15680967. S2CID 33220937.
^Weinreich M, Liang C, Chen HH, Stillman B (September 2001). "Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle". Proceedings of the National Academy of Sciences of the United States of America. 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. Bibcode:2001Natur.411.1068N. doi:10.1038/35082600. PMID 11429609. S2CID 4393812.
^Archambault V, Ikui AE, Drapkin BJ, Cross FR (August 2005). "Disruption of mechanisms that prevent rereplication triggers a DNA damage response". Molecular and Cellular Biology. 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. Bibcode:1996Natur.381..251T. doi:10.1038/381251a0. PMID 8622770. S2CID 4309206.
^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". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8361–7. Bibcode:2001PNAS...98.8361K. 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". Molecular Cell. 16 (6): 967–78. doi:10.1016/j.molcel.2004.11.038. PMID 15610739.
^Randell JC, Bowers JL, Rodríguez HK, Bell SP (January 2006). "Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase". Molecular 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, et al. (November 2006). "An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes". The EMBO Journal. 25 (21): 5150–8. doi:10.1038/sj.emboj.7601391. PMC 1630405. PMID 17053779.
In molecular biology, originrecognitioncomplex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in...
assembly of the pre-replication complex (pre-RC) is the binding of the originrecognitioncomplex (ORC) to the replication origin. In late mitosis, the Cdc6...
Zhao Y, et al. (July 2018). "Structure of the originrecognitioncomplex bound to DNA replication origin". Nature. 559 (7713): 217–222. Bibcode:2018Natur...
associate with the bound originrecognitioncomplex at the origin in order to form a larger complex necessary to load the Mcm complex onto the DNA. In eukaryotes...
Originrecognitioncomplex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein...
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the first high-resolution structures of both the MCM complex and the OriginRecognitionComplex (ORC) in 2015 and 2018. Tye is currently a Professor Emeritus...
pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, originrecognitioncomplexes (ORC1-6) recognize...
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proteins such as eukaryotic DNA (cytosine-5) methyltransferases, the originrecognitioncomplex 1 (Orc1) proteins, Bromo adjacent homology domain containing 1...
in Rrm3p code for a region that binds to Orc5, a domain in an originrecognitioncomplex. The binding of these two proteins appears to be linked to inappropriate...
Cellular model Eukaryotic DNA replication Mitotic catastrophe Originrecognitioncomplex Retinoblastoma protein Synchronous culture – synchronization of...
unwinding of origin DNA for precise timing. DnaA recognition sites in Escherichia coli are arranged in OriC to facilitate staged pre-replication complex assembling...
methyltransferase, methyl CpG binding protein MeCP2, and the originrecognitioncomplex protein ORC2. HP1 has a versatile structure with three main components;...
A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. Licensing factors primarily...
of Human OriginRecognitionComplex, Cdc6, and Minichromosome Maintenance Proteins during the Cell Cycle: Assembly of Prereplication Complexes in Late...
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