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Gene Review

ORC2  -  origin recognition complex subunit 2

Saccharomyces cerevisiae S288c

Synonyms: Origin recognition complex 71 kDa subunit, Origin recognition complex subunit 2, RRR1, SIR5, YBR0523, ...
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Disease relevance of ORC2

  • In an attempt to purify recombinant human ORC from insect cells infected with baculoviruses expressing HsORC subunits, we found that human ORC2, -3, -4, and -5 form a core complex [1].

High impact information on ORC2


Biological context of ORC2

  • To study the function of the ORC during defined cell cycle periods, we performed cell cycle execution point analyses with strains containing a conditional mutation in the ORC1, ORC2 or ORC5 subunit of ORC [4].
  • Characterization of an essential Orc2p-associated factor that plays a role in DNA replication [5].
  • RRR1/ORC2 is an essential gene, but the rrr1-316 allele, which is viable, is defective in the replication of nuclear DNA and the maintenance of the 2-microns episomal DNA [6].
  • Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L [7].
  • The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes [8].

Anatomical context of ORC2

  • Although Northern blot analysis of various adult mouse tissues found the highest levels of expression of ORC2-like (ORC2L) RNA in testes, strong signals did not always correspond to tissues in which high levels of DNA replication would be expected [7].
  • HsMcm10 associated with human Orc2 protein when overexpressed in COS-1 cells [9].
  • Depletion of Orc2 and Mcm3 by siRNA leads to an inhibition of cell proliferation, an altered cell cycle distribution as well as to multinucleated cells with insufficiently organised microtubules [10].
  • Using chromatin from HeLa cells in G1 phase, antibodies against Orc2p as well as antibodies against Mcm proteins specifically immunoprecipitate chromatin enriched for a DNA region that includes a replication origin [11].
  • Replicating macronuclei stained with Orc2 antibodies throughout development in wild-type cells but failed to do so in the amplification-defective rmm11 mutant [12].

Associations of ORC2 with chemical compounds


Physical interactions of ORC2

  • CDC45 also interacts genetically with ORC2, the gene encoding the second subunit of the origin recognition complex, ORC, and MCM3, another member of the MCM family [14].
  • We demonstrate through both immunoprecipitation and two-hybrid assays that a domain comprising the first 296 aa of Dbf4p interacts with Orc2p and Orc3p subunits of the origin recognition complex (ORC) [15].

Other interactions of ORC2

  • Cdc7p, like Oaf1p, also interacts with Orc2p in two-hybrid assays [5].
  • In plants, however, the only cloned putative homologs of ORC subunits are the Arabidopsis ORC2 and the rice ORC1 [16].
  • PKA was not required for the assembly of ORC2, Cdc6 and MCM3 onto chromatin [17].
  • This mutant is unable to maintain interactions with either Mcm2 or Orc2 at the semipermissive temperature of 30 degrees C, while the interaction with Rad53 is preserved [18].
  • The sir5-2 mutation is unlinked to sir1-1, yet the two mutations do not complement each other: mata1/MAT alpha sir5-2/SIR5 SIR1/sir1-1 diploids are capable of sporulation [19].

Analytical, diagnostic and therapeutic context of ORC2


  1. Architecture of the human origin recognition complex. Dhar, S.K., Delmolino, L., Dutta, A. J. Biol. Chem. (2001) [Pubmed]
  2. The Origin Recognition Complex Functions in Sister-Chromatid Cohesion in Saccharomyces cerevisiae. Shimada, K., Gasser, S.M. Cell (2007) [Pubmed]
  3. Role for a Xenopus Orc2-related protein in controlling DNA replication. Carpenter, P.B., Mueller, P.R., Dunphy, W.G. Nature (1996) [Pubmed]
  4. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Gibson, D.G., Bell, S.P., Aparicio, O.M. Genes Cells (2006) [Pubmed]
  5. Characterization of an essential Orc2p-associated factor that plays a role in DNA replication. Hardy, C.F. Mol. Cell. Biol. (1996) [Pubmed]
  6. Yeast origin recognition complex is involved in DNA replication and transcriptional silencing. Micklem, G., Rowley, A., Harwood, J., Nasmyth, K., Diffley, J.F. Nature (1993) [Pubmed]
  7. Mouse and human homologues of the yeast origin of replication recognition complex subunit ORC2 and chromosomal localization of the cognate human gene ORC2L. Takahara, K., Bong, M., Brevard, R., Eddy, R.L., Haley, L.L., Sait, S.J., Shows, T.B., Hoffman, G.G., Greenspan, D.S. Genomics (1996) [Pubmed]
  8. The origin recognition complex in silencing, cell cycle progression, and DNA replication. Loo, S., Fox, C.A., Rine, J., Kobayashi, R., Stillman, B., Bell, S. Mol. Biol. Cell (1995) [Pubmed]
  9. The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. Izumi, M., Yanagi, K., Mizuno, T., Yokoi, M., Kawasaki, Y., Moon, K.Y., Hurwitz, J., Yatagai, F., Hanaoka, F. Nucleic Acids Res. (2000) [Pubmed]
  10. Mouse pre-replicative complex proteins colocalise and interact with the centrosome. Stuermer, A., Hoehn, K., Faul, T., Auth, T., Brand, N., Kneissl, M., P??tter, V., Grummt, F. Eur. J. Cell Biol. (2007) [Pubmed]
  11. Human Mcm proteins at a replication origin during the G1 to S phase transition. Schaarschmidt, D., Ladenburger, E.M., Keller, C., Knippers, R. Nucleic Acids Res. (2002) [Pubmed]
  12. Characterization of a novel origin recognition complex-like complex: implications for DNA recognition, cell cycle control, and locus-specific gene amplification. Mohammad, M., York, R.D., Hommel, J., Kapler, G.M. Mol. Cell. Biol. (2003) [Pubmed]
  13. Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae. Garber, P.M., Rine, J. Genetics (2002) [Pubmed]
  14. Identification of Cdc45p, an essential factor required for DNA replication. Hardy, C.F. Gene (1997) [Pubmed]
  15. An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing. Duncker, B.P., Shimada, K., Tsai-Pflugfelder, M., Pasero, P., Gasser, S.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Putative subunits of the maize origin of replication recognition complex ZmORC1-ZmORC5. Witmer, X., Alvarez-Venegas, R., San-Miguel, P., Danilevskaya, O., Avramova, Z. Nucleic Acids Res. (2003) [Pubmed]
  17. Protein kinase A is required for chromosomal DNA replication. Costanzo, V., Avvedimento, E.V., Gottesman, M.E., Gautier, J., Grieco, D. Curr. Biol. (1999) [Pubmed]
  18. A mutation in Dbf4 motif M impairs interactions with DNA replication factors and confers increased resistance to genotoxic agents. Varrin, A.E., Prasad, A.A., Scholz, R.P., Ramer, M.D., Duncker, B.P. Mol. Cell. Biol. (2005) [Pubmed]
  19. Mutations leading to expression of the cryptic HMRa locus in the yeast Saccharomyces cerevisiae. Kassir, Y., Simchen, G. Genetics (1985) [Pubmed]
  20. The k43 gene, required for chorion gene amplification and diploid cell chromosome replication, encodes the Drosophila homolog of yeast origin recognition complex subunit 2. Landis, G., Kelley, R., Spradling, A.C., Tower, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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