Alternative titles; symbols
HGNC Approved Gene Symbol: ORC5
Cytogenetic location: 7q22.1-q22.2 Genomic coordinates (GRCh38): 7:104,126,341-104,208,013 (from NCBI)
DNA replication in eukaryotic cells is tightly controlled and coordinated with other events during the cell cycle and cell proliferation. Studies in Saccharomyces cerevisiae led to the identification of the 6-subunit origin recognition complex (ORC), which plays an essential role in the initiation of chromosome DNA replication and transcriptional silencing in budding yeast. ORC binds in an ATP-dependent manner to several well-defined autonomously replicating sequences that serve as the chromosomal replication origins. The genes for all 6 ORC subunits have been isolated, and deletion of any 1 of these genes results in lethality. Ishiai et al. (1997) cloned cDNAs from both human and fission yeast Schizosaccharomyces pombe that encode proteins homologous to the budding yeast and Drosophila Orc5. The predicted human protein shares 35.1, 22.3, and 19.4% identity with Drosophila, S. pombe, and S. cerevisiae Orc5, respectively.
Quintana et al. (1998) independently cloned ORC5. The bulk of human ORC5 protein was found in an insoluble nuclear fraction, whereas other human ORC subunits (e.g., ORC1; 601902) were easily extracted in the nuclear-soluble fractions and in S100. Quintana et al. (1998) also identified an ORC5 alternatively spliced mRNA. ORC5 transcripts were abundant in spleen, ovary, and prostate, in addition to tissues with high levels of DNA replication, like testis and colon mucosa, implicating human ORC proteins in functions other than DNA replication.
Quintana et al. (1998) found that the protein produced by alternatively spliced ORC5 formed a complex with ORC4 (603056), but not with ORC2 (601182), suggesting it may play a regulatory role in the assembly of different ORC subcomplexes.
Using Southern and PCR analysis of DNAs isolated from a panel of human/rodent somatic cell hybrids, Ishiai et al. (1997) mapped the ORC5 gene to chromosome 7. They refined the locus to 7q22 using fluorescence in situ hybridization. Further, they identified a YAC clone that contains the human ORC5L gene and maps to 7q22.1.
The region in which the ORC5 gene is located is frequently deleted in adult acute myeloid leukemia (AML; 601626) and myelodysplastic syndrome. Because of its localization and because of the implication of its protein product in cell cycle control (DNA replication) and regulation of gene expression (transcriptional silencing), Frohling et al. (2001) considered ORC5 as a candidate tumor suppressor gene for myeloid disorders. However, no mutations were found in the remaining ORC5 allele in 9 patients with AML or myelodysplastic syndrome who exhibited 7q22 deletions. Allelic expression analysis indicated that ORC5 is not imprinted. These data suggested that ORC5 does not function as a tumor suppressor in patients with myeloid neoplasms.
Frohling, S., Nakabayashi, K., Scherer, S. W., Dohner, H., Dohner, K. Mutation analysis of the origin recognition complex subunit 5 (ORC5L) gene in adult patients with myeloid leukemias exhibiting deletions of chromosome band 7q22. Hum. Genet. 108: 304-309, 2001. [PubMed: 11379876] [Full Text: https://doi.org/10.1007/s004390100498]
Ishiai, M., Dean, F. B., Okumura, K., Abe, M., Moon, K.-Y., Amin, A. A., Kagotani, K., Taguchi, H., Murakami, Y., Hanaoka, F., O'Donnell, M., Hurwitz, J., Eki, T. Isolation of human and fission yeast homologues of the budding yeast origin recognition complex subunit ORC5: human homologue (ORC5L) maps to 7q22. Genomics 46: 294-298, 1997. [PubMed: 9417919] [Full Text: https://doi.org/10.1006/geno.1997.5003]
Quintana, D. G., Thome, K. C., Hou, Z., Ligon, A. H., Morton, C. C., Dutta, A. ORC5L, a new member of the human origin recognition complex, is deleted in uterine leiomyomas and malignant myeloid diseases. J. Biol. Chem. 273: 27137-27145, 1998. [PubMed: 9765232] [Full Text: https://doi.org/10.1074/jbc.273.42.27137]