ORC1

Origin recognition complex, subunit 1

Identifiers

ORC1 ; HSORC1; ORC1L; PARC1

External IDs

OMIM: 601902 MGI: 1328337 HomoloGene: 31221 GeneCards: ORC1 Gene

Gene ontology
Molecular function	• DNA binding • chromatin binding • protein binding • ATP binding
Cellular component	• origin recognition complex • nucleus • nucleoplasm • nuclear origin of replication recognition complex • nucleolus • cytoplasm • cytosol • plasma membrane
Biological process	• G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S transition of mitotic cell cycle • mitotic cell cycle • DNA replication • DNA replication initiation • positive regulation of smooth muscle cell proliferation • positive regulation of G0 to G1 transition
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
52.37 – 52.4 Mb

Chr 4:
108.58 – 108.61 Mb

PubMed search

Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene.^[1]^[2]

Function

The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of the pre-replication complex, which includes additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the origin recognition complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MYST2/HBO1), a protein involved in control of transcription silencing.^[2]

Interactions

ORC1 has been shown to interact with:

CDC45-related protein^[3] and
CDC6,^[3]^[4]
Cell division cycle 7-related protein kinase,^[3]
Cyclin-dependent kinase 2,^[5]
MCM2,^[3]
MCM4,^[3]
MCM6,^[3]
MCM7,^[3]
MYST2,^[6]
ORC2,^[3]^[7]^[8]^[5]
ORC4,^[3]
ORC5,^[3] and
SKP2.^[5]

References

↑ Eki T, Okumura K, Amin A, Ishiai M, Abe M, Nogami M, Taguchi H, Hurwitz J, Murakami Y, Hanaoka F (Sep 1996). "Mapping of the human homologue (ORC1L) of the yeast origin recognition complex subunit 1 gene to chromosome band 1p32". Genomics 36 (3): 559–61. doi:10.1006/geno.1996.0511. PMID 8884289.
1 2 "Entrez Gene: ORC1L origin recognition complex, subunit 1-like (yeast)".
1 2 3 4 5 6 7 8 9 10 Kneissl M, Pütter V, Szalay AA, Grummt F (Mar 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". Journal of Molecular Biology 327 (1): 111–28. doi:10.1016/s0022-2836(03)00079-2. PMID 12614612.
↑ Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A (May 1998). "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase". Molecular and Cellular Biology 18 (5): 2758–67. doi:10.1128/mcb.18.5.2758. PMC 110655. PMID 9566895.
1 2 3 Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B (Mar 2002). "Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication". Molecular Cell 9 (3): 481–91. doi:10.1016/s1097-2765(02)00467-7. PMID 11931757.
↑ Iizuka M, Stillman B (Aug 1999). "Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein". The Journal of Biological Chemistry 274 (33): 23027–34. doi:10.1074/jbc.274.33.23027. PMID 10438470.
↑ Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T (Mar 2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells". The Journal of Biological Chemistry 277 (12): 10354–61. doi:10.1074/jbc.M111398200. PMID 11779870.
↑ Vashee S, Simancek P, Challberg MD, Kelly TJ (Jul 2001). "Assembly of the human origin recognition complex". The Journal of Biological Chemistry 276 (28): 26666–73. doi:10.1074/jbc.M102493200. PMID 11323433.

Gavin KA, Hidaka M, Stillman B (Dec 1995). "Conserved initiator proteins in eukaryotes". Science 270 (5242): 1667–71. doi:10.1126/science.270.5242.1667. PMID 7502077.
Ohtani K, DeGregori J, Leone G, Herendeen DR, Kelly TJ, Nevins JR (Dec 1996). "Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor". Molecular and Cellular Biology 16 (12): 6977–84. doi:10.1128/mcb.16.12.6977. PMC 231701. PMID 8943353.
Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A (May 1998). "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase". Molecular and Cellular Biology 18 (5): 2758–67. doi:10.1128/mcb.18.5.2758. PMC 110655. PMID 9566895.
Iizuka M, Stillman B (Aug 1999). "Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein". The Journal of Biological Chemistry 274 (33): 23027–34. doi:10.1074/jbc.274.33.23027. PMID 10438470.
Jiang W, McDonald D, Hope TJ, Hunter T (Oct 1999). "Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication". The EMBO Journal 18 (20): 5703–13. doi:10.1093/emboj/18.20.5703. PMC 1171637. PMID 10523313.
Tatsumi Y, Tsurimoto T, Shirahige K, Yoshikawa H, Obuse C (Feb 2000). "Association of human origin recognition complex 1 with chromatin DNA and nuclease-resistant nuclear structures". The Journal of Biological Chemistry 275 (8): 5904–10. doi:10.1074/jbc.275.8.5904. PMID 10681582.
Thome KC, Dhar SK, Quintana DG, Delmolino L, Shahsafaei A, Dutta A (Nov 2000). "Subsets of human origin recognition complex (ORC) subunits are expressed in non-proliferating cells and associate with non-ORC proteins". The Journal of Biological Chemistry 275 (45): 35233–41. doi:10.1074/jbc.M005765200. PMID 10954718.
Vashee S, Simancek P, Challberg MD, Kelly TJ (Jul 2001). "Assembly of the human origin recognition complex". The Journal of Biological Chemistry 276 (28): 26666–73. doi:10.1074/jbc.M102493200. PMID 11323433.
Laman H, Peters G, Jones N (Dec 2001). "Cyclin-mediated export of human Orc1". Experimental Cell Research 271 (2): 230–7. doi:10.1006/excr.2001.5360. PMID 11716535.
Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T (Mar 2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells". The Journal of Biological Chemistry 277 (12): 10354–61. doi:10.1074/jbc.M111398200. PMID 11779870.
Ladenburger EM, Keller C, Knippers R (Feb 2002). "Identification of a binding region for human origin recognition complex proteins 1 and 2 that coincides with an origin of DNA replication". Molecular and Cellular Biology 22 (4): 1036–48. doi:10.1128/MCB.22.4.1036-1048.2002. PMC 134626. PMID 11809796.
Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B (Mar 2002). "Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication". Molecular Cell 9 (3): 481–91. doi:10.1016/S1097-2765(02)00467-7. PMID 11931757.
Kneissl M, Pütter V, Szalay AA, Grummt F (Mar 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". Journal of Molecular Biology 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. PMID 12614612.
Ohta S, Tatsumi Y, Fujita M, Tsurimoto T, Obuse C (Oct 2003). "The ORC1 cycle in human cells: II. Dynamic changes in the human ORC complex during the cell cycle". The Journal of Biological Chemistry 278 (42): 41535–40. doi:10.1074/jbc.M307535200. PMID 12909626.
Tatsumi Y, Ohta S, Kimura H, Tsurimoto T, Obuse C (Oct 2003). "The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1". The Journal of Biological Chemistry 278 (42): 41528–34. doi:10.1074/jbc.M307534200. PMID 12909627.
Abdurashidova G, Danailov MB, Ochem A, Triolo G, Djeliova V, Radulescu S, Vindigni A, Riva S, Falaschi A (Aug 2003). "Localization of proteins bound to a replication origin of human DNA along the cell cycle". The EMBO Journal 22 (16): 4294–303. doi:10.1093/emboj/cdg404. PMC 175794. PMID 12912926.
Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J (Jul 2004). "Self-assembling protein microarrays". Science 305 (5680): 86–90. doi:10.1126/science.1097639. PMID 15232106.
Lidonnici MR, Rossi R, Paixão S, Mendoza-Maldonado R, Paolinelli R, Arcangeli C, Giacca M, Biamonti G, Montecucco A (Oct 2004). "Subnuclear distribution of the largest subunit of the human origin recognition complex during the cell cycle". Journal of Cell Science 117 (Pt 22): 5221–31. doi:10.1242/jcs.01405. PMID 15454574.

DNA replication (comparing Prokaryotic to Eukaryotic)

Initiation

Prokaryotic (initiation)	Pre-replication complex dnaC Cdc6 Helicase dnaA dnaB T7 Primase dnaG

Eukaryotic (preparation in G1 phase)	Pre-replication complex Origin recognition complex ORC1 ORC2 ORC3 ORC4 ORC5 ORC6 Cdc6 Cdt1 Minichromosome maintenance MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 Licensing factor Autonomously replicating sequence Single-strand binding protein SSBP2 SSBP3 SSBP4 RNase H RNASEH1 RNASEH2A Helicase: HFM1 Primase: PRIM1 PRIM2

Both	Origin of replication/Ori/Replicon Replication fork Lagging and leading strands Okazaki fragments Primer

Replication

Prokaryotic (elongation)	DNA polymerase III holoenzyme dnaC dnaE dnaH dnaN dnaQ dnaT dnaX holA holB holC holD holE Replisome DNA ligase DNA clamp Topoisomerase DNA gyrase Prokaryotic DNA polymerase: DNA polymerase I Klenow fragment

Eukaryotic (synthesis in S phase)	Replication factor C RFC1 Flap endonuclease FEN1 Topoisomerase Replication protein A RPA1 Eukaryotic DNA polymerase: alpha POLA1 POLA2 PRIM1 PRIM2 delta POLD1 POLD2 POLD3 POLD4 epsilon POLE POLE2 POLE3 POLE4 DNA clamp PCNA Control of chromosome duplication

Both	Movement: Processivity DNA ligase

Termination

Telomere: Telomerase
- TERT
- TERC
- DKC1

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ORC1

Function

Interactions

References

Further reading