The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ORC2  -  origin recognition complex, subunit 2

Homo sapiens

Synonyms: ORC2L, Origin recognition complex subunit 2
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ORC2L

  • Cells carrying this mutation failed to support the replication of a plasmid bearing the oriP replicator of Epstein Barr virus (EBV), and this defect was rescued by reintroduction of Orc2 [1].

High impact information on ORC2L


Biological context of ORC2L

  • Consistent with a role of CDC45L protein in the initiation of DNA replication it co-immunoprecipitates from cell extracts with a putative replication initiator protein, human ORC2L [4].
  • Analyses of somatic cell hybrid DNA and fluorescence in situ hybridization were employed to map the human ORC2L gene to chromosome 2q33 [5].
  • Cdc6 binding mirrored that of Orc2 in G(1)-arrested cells but decreased in asynchronous or M-phase cells [6].
  • Here we use two different approaches to investigate the presence of the human ORC2 protein and of Mcm proteins on chromatin of HeLa cells in various cell cycle phases [7].
  • Under digestion conditions when Mcm proteins were almost entirely released from chromatin, ORC2 protein was found to be associated with chromatin fragments containing several hundred base pairs of DNA [7].

Anatomical context of ORC2L

  • To study the assembly and function of mammalian ORC proteins in their native environment, HeLa cells were constructed that constitutively expressed an epitope-tagged, recombinant human Orc2 subunit that had been genetically altered [8].

Associations of ORC2L with chemical compounds

  • Previously shown to cause histone hyperacetylation and delocalization of replication initiation, trichostatin A treatment of cells led to a parallel qualitative change in the distribution of Mcm3, but not Orc2, across the c-myc replicator [6].
  • Second, we used an in vivo cross-linking procedure to covalently link Mcm proteins and ORC2 to DNA by short exposure of intact HeLa cells to formaldehyde [7].
  • Molecular combing of bromodeoxyuridine-labeled DNA revealed that once the Orc2 hypomorphic cells enter S-phase, fork density and fork progression are approximately comparable with wild type cells [9].
  • 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 [10].

Physical interactions of ORC2L

  • Furthermore, Orc2 was tightly bound to heterochromatin and heterochromatin protein 1alpha (HP1alpha) and HP1beta in G1 and early S phase, but during late S, G2 and M phases tight chromatin association was restricted to centromeres [3].

Regulatory relationships of ORC2L

  • We have previously reported generation of an Orc2 hypomorph cell line (Delta/-) that expresses very low levels of Orc2 but is viable [9].

Other interactions of ORC2L

  • The precise nucleotide of binding was identified for the two ORC and the CDC6 proteins near the start sites for leading-strand synthesis; the transition from the pre- to the post-replicative complex is accompanied by a 17 bp displacement of the ORC2 protein towards the start site [11].
  • Therefore, the low level of Orc2 hinders normal cell cycle progression by delaying the activation of G1 cyclin-dependent kinases [9].
  • These results demonstrate an unexpected role of ORC2 in CDK2 activation, a linkage that could be important for maintaining genomic stability [12].
  • 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 [13].
  • Cellular extraction revealed that the proportion of ORC2 and ORC4 subunits bound to chromatin was similar in all three cell lines throughout the cell-cycle [14].

Analytical, diagnostic and therapeutic context of ORC2L


  1. Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin. Dhar, S.K., Yoshida, K., Machida, Y., Khaira, P., Chaudhuri, B., Wohlschlegel, J.A., Leffak, M., Yates, J., Dutta, A. Cell (2001) [Pubmed]
  2. 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]
  3. Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance. Prasanth, S.G., Prasanth, K.V., Siddiqui, K., Spector, D.L., Stillman, B. EMBO J. (2004) [Pubmed]
  4. The human homolog of Saccharomyces cerevisiae CDC45. Saha, P., Thome, K.C., Yamaguchi, R., Hou, Z., Weremowicz, S., Dutta, A. J. Biol. Chem. (1998) [Pubmed]
  5. 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]
  6. Differential binding of replication proteins across the human c-myc replicator. Ghosh, M., Kemp, M., Liu, G., Ritzi, M., Schepers, A., Leffak, M. Mol. Cell. Biol. (2006) [Pubmed]
  7. Human minichromosome maintenance proteins and human origin recognition complex 2 protein on chromatin. Ritzi, M., Baack, M., Musahl, C., Romanowski, P., Laskey, R.A., Knippers, R. J. Biol. Chem. (1998) [Pubmed]
  8. Genetic analysis of human Orc2 reveals specific domains that are required in vivo for assembly and nuclear localization of the origin recognition complex. Radichev, I., Kwon, S.W., Zhao, Y., DePamphilis, M.L., Vassilev, A. J. Biol. Chem. (2006) [Pubmed]
  9. Proliferating human cells hypomorphic for origin recognition complex 2 and pre-replicative complex formation have a defect in p53 activation and Cdk2 kinase activation. Teer, J.K., Machida, Y.J., Labit, H., Novac, O., Hyrien, O., Marheineke, K., Zannis-Hadjopoulos, M., Dutta, A. J. Biol. Chem. (2006) [Pubmed]
  10. 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]
  11. Localization of proteins bound to a replication origin of human DNA along the cell cycle. Abdurashidova, G., Danailov, M.B., Ochem, A., Triolo, G., Djeliova, V., Radulescu, S., Vindigni, A., Riva, S., Falaschi, A. EMBO J. (2003) [Pubmed]
  12. Acute reduction of an origin recognition complex (ORC) subunit in human cells reveals a requirement of ORC for Cdk2 activation. Machida, Y.J., Teer, J.K., Dutta, A. J. Biol. Chem. (2005) [Pubmed]
  13. 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]
  14. Overexpression of ORC subunits and increased ORC-chromatin association in transformed mammalian cells. McNairn, A.J., Gilbert, D.M. J. Cell. Biochem. (2005) [Pubmed]
  15. Identification and functional analysis of a human homologue of the monkey replication origin ors8. Callejo, M., Sibani, S., Di Paola, D., Price, G.G., Zannis-Hadjopoulos, M. J. Cell. Biochem. (2006) [Pubmed]
  16. Interaction between HP1alpha and replication proteins in mammalian cells. Auth, T., Kunkel, E., Grummt, F. Exp. Cell Res. (2006) [Pubmed]
  17. Cloning and characterization of OsORC2, a new member of rice origin recognition complex. Li, K.G., Yang, J.S., Attia, K., Su, W., He, G.M., Qian, X.Y. Biotechnol. Lett. (2005) [Pubmed]
WikiGenes - Universities