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Gene Review

ORC1  -  origin recognition complex, subunit 1

Homo sapiens

Synonyms: HSORC1, ORC1L, Origin recognition complex subunit 1, PARC1, Replication control protein 1
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Disease relevance of ORC1L


High impact information on ORC1L

  • Other hORC subunits are stable throughout the cell cycle [6].
  • The BAH domain was not required for nuclear localization of Orc1, association of Orc1 with other ORC subunits, or selective degradation of Orc1 during S-phase [1].
  • The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo [1].
  • Green fluorescent protein-tagged ORC1 associated with chromatin throughout mitosis in living cells and co-localized with ORC4 in metaphase spreads [7].
  • Mutations in the Walker A motif of Orc1p, Orc4p, or Orc5p reduced the binding efficiency of HsORC1-5 modestly (2- to 5-fold) [8].

Biological context of ORC1L

  • Mapping of the human homologue (ORC1L) of the yeast origin recognition complex subunit 1 gene to chromosome band 1p32 [9].
  • Sequences corresponding to the intergenic region are highly abundant in a fraction of nascent DNA strands, strongly suggesting that this region not only harbors the binding sites for Orc1 protein and Orc2 protein but also serves as an origin of bidirectional DNA replication [10].
  • Interestingly, the less stable association occurred concomitantly with hyperphosphorylation of hORC1, suggesting that this hyperphosphorylation may be involved in M phase changes [11].
  • An artificial reduction in the level of ORC1 in human cells by RNA interference results in a shift of ORC2 to the nuclease-soluble fraction, and the association of MCM proteins with chromatin fractions is also blocked by this treatment [12].
  • Fluorescence resonance energy transfer (FRET) experiments demonstrate the interaction of human Orc1p and HP1 in vivo [13].

Anatomical context of ORC1L

  • The level of the largest subunit of human ORC (ORC1) during the cell cycle was studied in several human cell lines with a specific antibody [14].
  • The behavior of ORC components in human cell nuclei with respect to the ORC1 cycle demonstrates that ORCs 2-5 form a complex that is present throughout the cell cycle and that associates with ORC1 when it accumulates in G1 nuclei [12].
  • In proliferating mammalian cells, ORC activity appears to be regulated by reducing the affinity of the Orc1 subunit for chromatin during S phase and then preventing reformation of a stable ORC-chromatin complex until mitosis is completed and a nuclear membrane is assembled [15].
  • Cell-cycle-dependent variation in Orc1/Cdc6 levels has been demonstrated, reminiscent of variations in cyclin levels during the eukaryotic cell cycle [16].
  • ORC subunits 2 and 4 were highly overexpressed in both HeLa and VA13, whereas ORC1 levels were elevated in VA13 but considerably higher in HeLa cells [17].

Associations of ORC1L with chemical compounds

  • Two isoforms of the human ornithine carrier, ORC1 and ORC2, have been identified by overexpression of the proteins in bacteria and by study of the transport properties of the purified proteins reconstituted into liposomes [18].
  • AIM: To compare the rates of orthodontic space closure for: Active ligatures, polyurethane powerchain (Rocky Mountain Orthodontics, RMO Europe, Parc d'Innovation, Rue Geiler de Kaysersberg, 67400 Illkirch-Graffenstaden, Strasbourg, France) and nickel titanium springs [19].

Regulatory relationships of ORC1L

  • Indeed, the subnuclear distribution of Orc1p is not affected by treatments that trigger the dispersal of HP1 [13].

Other interactions of ORC1L

  • Cyclin-mediated export of human Orc1 [20].
  • Our data suggest a role of HP1 in the recruitment but not in the stable association of Orc1p with heterochromatin [13].
  • ORC1 accumulates in G1 and is degraded in S phase, although other ORC subunits (ORCs 2-5) remain at almost constant levels [12].
  • MCM7 is recruited to multiple sites in chromatin in S and G(2), at which time it is not detected with ORC1 [21].
  • Here we show that part of the mechanism by which this is accomplished is the selective association of Orc1 with Cdk1 (Cdc2)/cyclin A during the G(2)/M phase of cell division [15].

Analytical, diagnostic and therapeutic context of ORC1L

  • For this purpose, we performed chromatin immunoprecipitation assays with antibodies against human Orc1 and Orc2 proteins [10].
  • This behavior mimicked the increased concentration and perinuclear accumulation of endogenous Orc1 in apoptotic cells that arise spontaneously in proliferating cell cultures [22].
  • Using the yeast two-hybrid system and immunoprecipitation, we report here that murine HP1alpha interacts with the preRC proteins ORC1, ORC2 and CDC6 [23].
  • PARC and PTRC were measured by immunoradiometric assays [24].
  • J. P. Lecocq Conference on gene therapy. 5-7 July 1994 Ecole Superieure de Biotechnologie de Strasbourg, Pole API, Parc d'Innovation, Illkirch, Nr Strasbourg, France [25].


  1. The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo. Noguchi, K., Vassilev, A., Ghosh, S., Yates, J.L., Depamphilis, M.L. EMBO J. (2006) [Pubmed]
  2. Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Boot, R.G., Verhoek, M., de Fost, M., Hollak, C.E., Maas, M., Bleijlevens, B., van Breemen, M.J., van Meurs, M., Boven, L.A., Laman, J.D., Moran, M.T., Cox, T.M., Aerts, J.M. Blood (2004) [Pubmed]
  3. The Ews/Fli-1 fusion gene changes the status of p53 in neuroblastoma tumor cell lines. Rorie, C.J., Weissman, B.E. Cancer Res. (2004) [Pubmed]
  4. CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis. Pardo, A., Smith, K.M., Abrams, J., Coffman, R., Bustos, M., McClanahan, T.K., Grein, J., Murphy, E.E., Zlotnik, A., Selman, M. J. Leukoc. Biol. (2001) [Pubmed]
  5. Human papillomavirus type 16 DNA expresses a replication modulation factor in cos-1 cells. Hecht, E.M., Chesters, P.M., McCance, D.J. J. Gen. Virol. (1990) [Pubmed]
  6. Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Méndez, J., Zou-Yang, X.H., Kim, S.Y., Hidaka, M., Tansey, W.P., Stillman, B. Mol. Cell (2002) [Pubmed]
  7. Stability, chromatin association and functional activity of mammalian pre-replication complex proteins during the cell cycle. Okuno, Y., McNairn, A.J., den Elzen, N., Pines, J., Gilbert, D.M. EMBO J. (2001) [Pubmed]
  8. Studies of the properties of human origin recognition complex and its Walker A motif mutants. Giordano-Coltart, J., Ying, C.Y., Gautier, J., Hurwitz, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Mapping of the human homologue (ORC1L) of the yeast origin recognition complex subunit 1 gene to chromosome band 1p32. Eki, T., Okumura, K., Amin, A., Ishiai, M., Abe, M., Nogami, M., Taguchi, H., Hurwitz, J., Murakami, Y., Hanaoka, F. Genomics (1996) [Pubmed]
  10. Identification of a binding region for human origin recognition complex proteins 1 and 2 that coincides with an origin of DNA replication. Ladenburger, E.M., Keller, C., Knippers, R. Mol. Cell. Biol. (2002) [Pubmed]
  11. Association of human origin recognition complex 1 with chromatin DNA and nuclease-resistant nuclear structures. Tatsumi, Y., Tsurimoto, T., Shirahige, K., Yoshikawa, H., Obuse, C. J. Biol. Chem. (2000) [Pubmed]
  12. The ORC1 cycle in human cells: II. Dynamic changes in the human ORC complex during the cell cycle. Ohta, S., Tatsumi, Y., Fujita, M., Tsurimoto, T., Obuse, C. J. Biol. Chem. (2003) [Pubmed]
  13. Subnuclear distribution of the largest subunit of the human origin recognition complex during the cell cycle. Lidonnici, M.R., Rossi, R., Paixão, S., Mendoza-Maldonado, R., Paolinelli, R., Arcangeli, C., Giacca, M., Biamonti, G., Montecucco, A. J. Cell. Sci. (2004) [Pubmed]
  14. The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1. Tatsumi, Y., Ohta, S., Kimura, H., Tsurimoto, T., Obuse, C. J. Biol. Chem. (2003) [Pubmed]
  15. Role for Cdk1 (Cdc2)/cyclin A in preventing the mammalian origin recognition complex's largest subunit (Orc1) from binding to chromatin during mitosis. Li, C.J., Vassilev, A., DePamphilis, M.L. Mol. Cell. Biol. (2004) [Pubmed]
  16. Archaeal cell cycle progress. Lundgren, M., Bernander, R. Curr. Opin. Microbiol. (2005) [Pubmed]
  17. Overexpression of ORC subunits and increased ORC-chromatin association in transformed mammalian cells. McNairn, A.J., Gilbert, D.M. J. Cell. Biochem. (2005) [Pubmed]
  18. The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. Fiermonte, G., Dolce, V., David, L., Santorelli, F.M., Dionisi-Vici, C., Palmieri, F., Walker, J.E. J. Biol. Chem. (2003) [Pubmed]
  19. A randomized clinical trial to compare three methods of orthodontic space closure. Dixon, V., Read, M.J., O'Brien, K.D., Worthington, H.V., Mandall, N.A. Journal of orthodontics. (2002) [Pubmed]
  20. Cyclin-mediated export of human Orc1. Laman, H., Peters, G., Jones, N. Exp. Cell Res. (2001) [Pubmed]
  21. Site-specific loading of an MCM protein complex in a DNA replication initiation zone upstream of the c-MYC gene in the HeLa cell cycle. Kinoshita, Y., Johnson, E.M. J. Biol. Chem. (2004) [Pubmed]
  22. Ubiquitylation, phosphorylation and Orc2 modulate the subcellular location of Orc1 and prevent it from inducing apoptosis. Saha, T., Ghosh, S., Vassilev, A., DePamphilis, M.L. J. Cell. Sci. (2006) [Pubmed]
  23. Interaction between HP1alpha and replication proteins in mammalian cells. Auth, T., Kunkel, E., Grummt, F. Exp. Cell Res. (2006) [Pubmed]
  24. Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature. Ohyama, K., Fujimoto, M., Nakagomi, Y., Ohta, M., Yamori, T., Kato, K. Horm. Res. (1991) [Pubmed]
  25. J. P. Lecocq Conference on gene therapy. 5-7 July 1994 Ecole Superieure de Biotechnologie de Strasbourg, Pole API, Parc d'Innovation, Illkirch, Nr Strasbourg, France. Meager, A. Biologicals (1995) [Pubmed]
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