origin recognition complex


Summary: The origin recognition complex is a multi-subunit DNA-binding protein that initiates DNA REPLICATION in eukaryotes.

Top Publications

  1. Lynch P, Fraser H, Sevastopoulos E, Rine J, Rusche L. Sum1p, the origin recognition complex, and the spreading of a promoter-specific repressor in Saccharomyces cerevisiae. Mol Cell Biol. 2005;25:5920-32 pubmed
    ..Finally, this study uncovered a functional connection between wild-type Sum1p and the origin recognition complex, and this relationship also contributes to mutant Sum1-1p localization.
  2. Xu W, Aparicio J, Aparicio O, Tavare S. Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae. BMC Genomics. 2006;7:276 pubmed
    ..cerevisiae, Autonomously Replicating Sequences (ARSs) contain a consensus sequence (ACS) that binds the Origin Recognition Complex (ORC) and is essential for origin function...
  3. Miller D, Grimwade J, Betteridge T, Rozgaja T, Torgue J, Leonard A. Bacterial origin recognition complexes direct assembly of higher-order DnaA oligomeric structures. Proc Natl Acad Sci U S A. 2009;106:18479-84 pubmed publisher
    ..We propose that in bacteria, DnaA oligomers of limited length and stability emerge from single high-affinity sites and extend toward weak sites to facilitate their loading as a key stage of prokaryotic pre-RC assembly. ..
  4. Balasov M, Huijbregts R, Chesnokov I. Functional analysis of an Orc6 mutant in Drosophila. Proc Natl Acad Sci U S A. 2009;106:10672-7 pubmed publisher
    The origin recognition complex (ORC) is a 6-subunit complex required for the initiation of DNA replication in eukaryotic organisms. ORC is also involved in other cell functions...
  5. Chastain P, Bowers J, Lee D, Bell S, Griffith J. Mapping subunit location on the Saccharomyces cerevisiae origin recognition complex free and bound to DNA using a novel nanoscale biopointer. J Biol Chem. 2004;279:36354-62 pubmed
    The Saccharomyces cerevisiae origin recognition complex (ORC) is composed of six subunits and is an essential component in the assembly of the replication apparatus...
  6. Mehra P, Biswas A, Gupta A, Gourinath S, Chitnis C, Dhar S. Expression and characterization of human malaria parasite Plasmodium falciparum origin recognition complex subunit 1. Biochem Biophys Res Commun. 2005;337:955-66 pubmed
    In eukaryotes, the origin recognition complex (ORC) is essential for the initiation of DNA replication. The largest subunit of this complex (ORC1) has a regulatory role in origin activation...
  7. Kaguni J. DnaA: controlling the initiation of bacterial DNA replication and more. Annu Rev Microbiol. 2006;60:351-75 pubmed
    ..The datA locus represents a third mechanism, which appears to influence the availability of DnaA protein in supporting rifampicin-resistant initiations. ..
  8. Minami H, Takahashi J, Suto A, Saitoh Y, Tsutsumi K. Binding of AlF-C, an Orc1-binding transcriptional regulator, enhances replicator activity of the rat aldolase B origin. Mol Cell Biol. 2006;26:8770-80 pubmed
    ..ChIP assays revealed that both replication origins bind AlF-C and Orc1. We think that the results presented here may represent one mode of origin recognition in mammalian cells. ..
  9. Thomae A, Pich D, Brocher J, Spindler M, Berens C, Hock R, et al. Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins. Proc Natl Acad Sci U S A. 2008;105:1692-7 pubmed publisher
    In all eukaryotic cells, origins of DNA replication are characterized by the binding of the origin recognition complex (ORC)...

More Information


  1. Davey M, Jeruzalmi D, Kuriyan J, O Donnell M. Motors and switches: AAA+ machines within the replisome. Nat Rev Mol Cell Biol. 2002;3:826-35 pubmed
    ..Other AAA+ proteins are also involved in the initiation of DNA replication, and studies of the E. coli clamp loader indicate mechanisms by which these proteins might function. ..
  2. Baldinger T, Gossen M. Binding of Drosophila ORC proteins to anaphase chromosomes requires cessation of mitotic cyclin-dependent kinase activity. Mol Cell Biol. 2009;29:140-9 pubmed publisher
    ..the acquisition of replication competence by eukaryotic chromosomes is the binding of the multisubunit origin recognition complex, ORC...
  3. Hizume K, Yagura M, Araki H. Concerted interaction between origin recognition complex (ORC), nucleosomes and replication origin DNA ensures stable ORC-origin binding. Genes Cells. 2013;18:764-79 pubmed publisher
    ..DNA replication is initiated, are determined in eukaryotic cells by specific binding of a six-subunit origin recognition complex (ORC). Many biochemical analyses have showed the detailed properties of the ORC-DNA interaction...
  4. Nievera C, Torgue J, Grimwade J, Leonard A. SeqA blocking of DnaA-oriC interactions ensures staged assembly of the E. coli pre-RC. Mol Cell. 2006;24:581-92 pubmed
    ..Thus, during the sequestration period, SeqA repressed pre-RC assembly while ensuring resetting of E. coli ORC. ..
  5. Atanassova N, Grainge I. Biochemical characterization of the minichromosome maintenance (MCM) protein of the crenarchaeote Aeropyrum pernix and its interactions with the origin recognition complex (ORC) proteins. Biochemistry. 2008;47:13362-70 pubmed publisher
    ..maintenance (MCM) homologue, presumed to be the replicative helicase and between one and three origin recognition complex (ORC) homologues involved in binding to the replication origins...
  6. Kumar S, Farhana A, Hasnain S. In-vitro helix opening of M. tuberculosis oriC by DnaA occurs at precise location and is inhibited by IciA like protein. PLoS ONE. 2009;4:e4139 pubmed publisher
    ..tb origin of replication. These results have a bearing on the functional role of the important regulator of M.tb chromosomal replication belonging to the LysR family of bacterial regulatory proteins in the context of latency. ..
  7. Dueber E, Corn J, Bell S, Berger J. Replication origin recognition and deformation by a heterodimeric archaeal Orc1 complex. Science. 2007;317:1210-3 pubmed publisher
    ..Biochemical and comparative analyses indicate that AAA+/DNA contacts observed in the structure are dynamic and evolutionarily conserved, suggesting that the complex forms a core component of the basal initiation machinery...
  8. Mancio Silva L, Rojas Meza A, Vargas M, Scherf A, Hernandez Rivas R. Differential association of Orc1 and Sir2 proteins to telomeric domains in Plasmodium falciparum. J Cell Sci. 2008;121:2046-53 pubmed publisher
    ..Our data suggest that Plasmodium telomeres might fold back and that Orc1 cooperates with Sir2 in telomeric silencing. ..
  9. Claycomb J, MacAlpine D, Evans J, Bell S, Orr Weaver T. Visualization of replication initiation and elongation in Drosophila. J Cell Biol. 2002;159:225-36 pubmed
    ..Bromodeoxyuridine, origin recognition complex, and the elongation factors minichromosome maintenance proteins (MCM)2-7 and proliferating cell nuclear ..
  10. Sun J, Kawakami H, Zech J, Speck C, Stillman B, Li H. Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy. Structure. 2012;20:534-44 pubmed publisher
    The eukaryotic origin recognition complex (ORC) interacts with and remodels origins of DNA replication prior to initiation in S phase...
  11. Grainge I, Scaife S, Wigley D. Biochemical analysis of components of the pre-replication complex of Archaeoglobus fulgidus. Nucleic Acids Res. 2003;31:4888-98 pubmed
    ..Licensing involves the interactions of a variety of proteins including the origin recognition complex (ORC), Cdc6 and the Mcm2-7 helicase, homologues of which are also found in archaea...
  12. Collinge M, Spillane C, Kohler C, Gheyselinck J, Grossniklaus U. Genetic interaction of an origin recognition complex subunit and the Polycomb group gene MEDEA during seed development. Plant Cell. 2004;16:1035-46 pubmed
    The eukaryotic origin recognition complex (ORC) is made up of six subunits and functions in nuclear DNA replication, chromatin structure, and gene silencing in both fungi and metazoans...
  13. Eaton M, Prinz J, MacAlpine H, Tretyakov G, Kharchenko P, MacAlpine D. Chromatin signatures of the Drosophila replication program. Genome Res. 2011;21:164-74 pubmed publisher
  14. Remus D, Beall E, Botchan M. DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC-DNA binding. EMBO J. 2004;23:897-907 pubmed
    Drosophila origin recognition complex (ORC) localizes to defined positions on chromosomes, and in follicle cells the chorion gene amplification loci are well-studied examples. However, the mechanism of specific localization is not known...
  15. Godoy P, Nogueira Junior L, Paes L, Cornejo A, Martins R, Silber A, et al. Trypanosome prereplication machinery contains a single functional orc1/cdc6 protein, which is typical of archaea. Eukaryot Cell. 2009;8:1592-603 pubmed publisher
    ..cerevisiae, and in multicellular organisms, the replication origin is recognized by the heterohexamer origin recognition complex (ORC) containing six proteins, Orc1 to Orc6, while in members of the domain Archaea, the replication ..
  16. Witmer X, Alvarez Venegas R, San Miguel P, Danilevskaya O, Avramova Z. Putative subunits of the maize origin of replication recognition complex ZmORC1-ZmORC5. Nucleic Acids Res. 2003;31:619-28 pubmed
    ..The isolation and molecular characterization of an ORC4-homologous gene from maize argues that, in its evolution, Arabidopsis may have lost the homologous ORC4 gene. ..
  17. Gaudier M, Schuwirth B, Westcott S, Wigley D. Structural basis of DNA replication origin recognition by an ORC protein. Science. 2007;317:1213-6 pubmed
    ..We report the structure of an archaeal origin recognition complex protein, ORC1, bound to an origin recognition box, a DNA sequence that is found in multiple copies at ..
  18. Costas C, de la Paz Sanchez M, Stroud H, Yu Y, Oliveros J, Feng S, et al. Genome-wide mapping of Arabidopsis thaliana origins of DNA replication and their associated epigenetic marks. Nat Struct Mol Biol. 2011;18:395-400 pubmed publisher
    ..Z, H3K4me2, H3K4me3 and H4K5ac, and depleted in H3K4me1 and H3K9me2. Our data help clarify the epigenetic specification of DNA replication origins in A. thaliana and have implications for other eukaryotes. ..
  19. Abdurashidova G, Danailov M, Ochem A, Triolo G, Djeliova V, Radulescu S, et al. Localization of proteins bound to a replication origin of human DNA along the cell cycle. EMBO J. 2003;22:4294-303 pubmed
  20. Donti T, Datta S, Sandoval P, Kapler G. Differential targeting of Tetrahymena ORC to ribosomal DNA and non-rDNA replication origins. EMBO J. 2009;28:223-33 pubmed publisher
    The Tetrahymena thermophila origin recognition complex (ORC) contains an integral RNA subunit, 26T RNA, which confers specificity to the amplified ribosomal DNA (rDNA) origin by base pairing with an essential cis-acting replication ..
  21. Randell J, Bowers J, Rodríguez H, Bell S. Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell. 2006;21:29-39 pubmed
    ..protein-DNA assembly is called the prereplicative complex (pre-RC), and its formation requires the origin recognition complex (ORC), Cdc6, Cdt1, and ATP. ATP hydrolysis by ORC is required for multiple rounds of Mcm2-7 loading...
  22. Hemerly A, Prasanth S, Siddiqui K, Stillman B. Orc1 controls centriole and centrosome copy number in human cells. Science. 2009;323:789-93 pubmed publisher
    ..We report a new role for the Orc1 protein, a subunit of the origin recognition complex (ORC) that is a key component of the DNA replication licensing machinery, in controlling centriole and ..
  23. Patterson S, Robert C, Whittle C, Chakrabarti R, Doerig C, Chakrabarti D. Pre-replication complex organization in the atypical DNA replication cycle of Plasmodium falciparum: characterization of the mini-chromosome maintenance (MCM) complex formation. Mol Biochem Parasitol. 2006;145:50-9 pubmed
    ..No phosphorylation of PfMCM2, 6 and 7 was detected, but two as yet unidentified threonine-phosphosphorylated proteins were present in the complex, whose pattern of phosphorylation varied during parasite development. ..
  24. Kasiviswanathan R, Shin J, Kelman Z. Interactions between the archaeal Cdc6 and MCM proteins modulate their biochemical properties. Nucleic Acids Res. 2005;33:4940-50 pubmed publisher
    The origin recognition complex, Cdc6 and the minichromosome maintenance (MCM) complex play essential roles in the initiation of eukaryotic DNA replication...
  25. Karnani N, Taylor C, Malhotra A, Dutta A. Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection. Mol Biol Cell. 2010;21:393-404 pubmed publisher
    ..Examination of a subset of these origins by chromatin immunoprecipitation against origin recognition complex (ORC) subunits 2 and 3 showed 93% of initiation peaks to localize at/within 1 kb of ORC binding sites...
  26. Hsu H, Stillman B, Xu R. Structural basis for origin recognition complex 1 protein-silence information regulator 1 protein interaction in epigenetic silencing. Proc Natl Acad Sci U S A. 2005;102:8519-24 pubmed
    The interaction between silence information regulator 1 protein (Sir1p) and origin recognition complex 1 protein (Orc1p), the largest subunit of the origin recognition complex, plays an important role in the establishment of ..
  27. Ozaydin B, Rine J. Expanded roles of the origin recognition complex in the architecture and function of silenced chromatin in Saccharomyces cerevisiae. Mol Cell Biol. 2010;30:626-39 pubmed publisher
    ..Each of the four silencers, which flank the silenced loci, includes an origin recognition complex (ORC) binding site (ACS). ORC directly interacted with Sir1 and recruits Sir1 to the silencers...
  28. Uchiyama M, Wang T. The B-subunit of DNA polymerase alpha-primase associates with the origin recognition complex for initiation of DNA replication. Mol Cell Biol. 2004;24:7419-34 pubmed
    ..Here, we show that the fission yeast Spb70 genetically interacts and coprecipitates with origin recognition complex proteins Orp1/Orc1 and Orp2/Orc2 and primase coupling subunit Spp2/p58...
  29. Hickman M, Froyd C, Rusche L. Reinventing heterochromatin in budding yeasts: Sir2 and the origin recognition complex take center stage. Eukaryot Cell. 2011;10:1183-92 pubmed publisher
    ..In addition, we highlight how this diversification has been facilitated by gene duplications and has contributed to adaptations in lifestyle. ..
  30. Huijbregts R, Svitin A, Stinnett M, Renfrow M, Chesnokov I. Drosophila Orc6 facilitates GTPase activity and filament formation of the septin complex. Mol Biol Cell. 2009;20:270-81 pubmed publisher
    The origin recognition complex or ORC is a six-subunit protein important for DNA replication and other cell functions...
  31. Prasanth S, Prasanth K, Stillman B. Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science. 2002;297:1026-31 pubmed
    b>Origin recognition complex (ORC) proteins serve as a landing pad for the assembly of a multiprotein prereplicative complex, which is required to initiate DNA replication...
  32. Shu M, Qin Y, Jiang M. RNA interference targeting ORC1 gene suppresses the proliferation of vascular smooth muscle cells in rats. Exp Mol Pathol. 2008;84:206-12 pubmed publisher
    ..The largest subunit of the origin recognition complex (ORC), ORC1, plays a critical role during the initiation of DNA replication in eukaryotes...
  33. Chesnokov I, Chesnokova O, Botchan M. A cytokinetic function of Drosophila ORC6 protein resides in a domain distinct from its replication activity. Proc Natl Acad Sci U S A. 2003;100:9150-5 pubmed
    ..We report that the smallest of Drosophila origin recognition complex subunits, Orc6, was found in embryos and cell culture localized to the cell membrane and cleavage furrow ..
  34. Gibson D, Bell S, Aparicio O. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells. 2006;11:557-73 pubmed
    ..In Saccharomyces cerevisiae, the origin recognition complex (ORC) binds replication origins throughout the cell cycle and participates in pre-RC assembly...
  35. Teer J, Machida Y, Labit H, Novac O, Hyrien O, Marheineke K, et al. Proliferating human cells hypomorphic for origin recognition complex 2 and pre-replicative complex formation have a defect in p53 activation and Cdk2 kinase activation. J Biol Chem. 2006;281:6253-60 pubmed
    The Origin Recognition Complex (ORC) is a critical component of replication initiation. We have previously reported generation of an Orc2 hypomorph cell line (Delta/-) that expresses very low levels of Orc2 but is viable...
  36. Ying C, Gautier J. The ATPase activity of MCM2-7 is dispensable for pre-RC assembly but is required for DNA unwinding. EMBO J. 2005;24:4334-44 pubmed
    ..These data establish that mutations affecting the ATPase activity of the MCM complex uncouple its role in pre-RC assembly from DNA replication. ..
  37. Tatsumi Y, Ohta S, Kimura H, Tsurimoto T, Obuse C. The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1. J Biol Chem. 2003;278:41528-34 pubmed
    Components of ORC (the origin recognition complex) are highly conserved among eukaryotes and are thought to play an essential role in the initiation of DNA replication...
  38. Gaczynska M, Osmulski P, Jiang Y, Lee J, Bermudez V, Hurwitz J. Atomic force microscopic analysis of the binding of the Schizosaccharomyces pombe origin recognition complex and the spOrc4 protein with origin DNA. Proc Natl Acad Sci U S A. 2004;101:17952-7 pubmed
    ..In eukaryotes, the initiation of DNA replication requires the interaction between origin sequences and the origin recognition complex (ORC), which is highly conserved...
  39. Prasanth S, Prasanth K, Siddiqui K, Spector D, Stillman B. Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. EMBO J. 2004;23:2651-63 pubmed
    The initiation of DNA replication in S phase requires the prior assembly of an origin recognition complex (ORC)-dependent pre-replicative complex on chromatin during G1 phase of the cell division cycle...
  40. Shin J, Grabowski B, Kasiviswanathan R, Bell S, Kelman Z. Regulation of minichromosome maintenance helicase activity by Cdc6. J Biol Chem. 2003;278:38059-67 pubmed
    ..Analysis of Cdc6 and MCM homologues from several archaea exhibited differences in the inhibitory activity suggesting divergence in function in Cdc6 and MCM homologues among the archaea...
  41. Guernsey D, Matsuoka M, Jiang H, Evans S, Macgillivray C, Nightingale M, et al. Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome. Nat Genet. 2011;43:360-4 pubmed publisher
    ..genes, we identified three different mutations in the gene encoding ORC4, a component of the eukaryotic origin recognition complex, in five individuals with Meier-Gorlin syndrome...
  42. Dueber E, Costa A, Corn J, Bell S, Berger J. Molecular determinants of origin discrimination by Orc1 initiators in archaea. Nucleic Acids Res. 2011;39:3621-31 pubmed publisher
    ..These loci are identified and bound by the origin recognition complex (ORC), and subsequently activated by a cascade of events that includes recruitment of an additional ..
  43. Takahashi N, Yamaguchi Y, Yamairi F, Makise M, Takenaka H, Tsuchiya T, et al. Analysis on origin recognition complex containing Orc5p with defective Walker A motif. J Biol Chem. 2004;279:8469-77 pubmed
    Orc5p is one of six proteins that make up the origin recognition complex (ORC), a candidate initiator of chromosomal DNA replication in eukaryotes...
  44. Li C, Vassilev A, DePamphilis M. Role for Cdk1 (Cdc2)/cyclin A in preventing the mammalian origin recognition complex's largest subunit (Orc1) from binding to chromatin during mitosis. Mol Cell Biol. 2004;24:5875-86 pubmed
    The eukaryotic origin recognition complex (ORC) selects the genomic sites where prereplication complexes are assembled and DNA replication begins...
  45. Aggarwal B, Calvi B. Chromatin regulates origin activity in Drosophila follicle cells. Nature. 2004;430:372-6 pubmed
    ..We find that histones at the active origins are hyperacetylated, coincident with binding of the origin recognition complex (ORC)...
  46. Giordano Coltart J, Ying C, Gautier J, Hurwitz J. Studies of the properties of human origin recognition complex and its Walker A motif mutants. Proc Natl Acad Sci U S A. 2005;102:69-74 pubmed
    The eukaryotic six-subunit origin recognition complex (ORC) governs the initiation site of DNA replication and formation of the prereplication complex...
  47. Edwards M, Tutter A, Cvetic C, Gilbert C, Prokhorova T, Walter J. MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts. J Biol Chem. 2002;277:33049-57 pubmed
    ..It is recruited to chromatin by the origin recognition complex (ORC), Cdc6, and Cdt1, and it is activated at the G(1)/S transition by Cdc45 and the protein kinases ..
  48. Hartl T, Boswell C, Orr Weaver T, Bosco G. Developmentally regulated histone modifications in Drosophila follicle cells: initiation of gene amplification is associated with histone H3 and H4 hyperacetylation and H1 phosphorylation. Chromosoma. 2007;116:197-214 pubmed
    ..b>Origin recognition complex subunit 2 (orc2) mutants with severe amplification defects do not abolish H4 acetylation, whereas the ..
  49. Tiengwe C, Marcello L, Farr H, Dickens N, Kelly S, Swiderski M, et al. Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. Cell Rep. 2012;2:185-97 pubmed publisher
    ..In addition, ORC1/CDC6 loss causes derepression of silent Variant Surface Glycoprotein genes, which are critical for host immune evasion. ..
  50. Sun J, Evrin C, Samel S, Fernández Cid A, Riera A, Kawakami H, et al. Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA. Nat Struct Mol Biol. 2013;20:944-51 pubmed publisher
    ..The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action. ..
  51. Kim J, Nordman J, Xie F, Kashevsky H, Eng T, Li S, et al. Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression. Genes Dev. 2011;25:1384-98 pubmed publisher
    ..to investigate these in vivo replicons with respect to parameters of transcription, localization of the origin recognition complex (ORC), and histone acetylation, yielding important insights into gene amplification as a metazoan ..
  52. Makise M, Takehara M, Kuniyasu A, Matsui N, Nakayama H, Mizushima T. Linkage between phosphorylation of the origin recognition complex and its ATP binding activity in Saccharomyces cerevisiae. J Biol Chem. 2009;284:3396-407 pubmed publisher
    ..Adenine nucleotides that bind to the origin recognition complex (ORC) are also suggested to be involved in this process...
  53. Weber J, Irlbacher H, Ehrenhofer Murray A. Control of replication initiation by the Sum1/Rfm1/Hst1 histone deacetylase. BMC Mol Biol. 2008;9:100 pubmed publisher
    ..Initiation requires binding of the replication initiator, the Origin Recognition Complex (ORC), to a consensus sequence within origins...