ORC1

Template:PBB Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene.

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.

Interactions

ORC1 has been shown to interact with:

• CDC45-related protein and
• CDC6,
• Cell division cycle 7-related protein kinase,
• Cyclin-dependent kinase 2,
• MCM2,
• MCM4,
• MCM6,
• MCM7,
• MYST2,
• ORC2,
• ORC4,
• ORC5, and
• SKP2.

Further reading

• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• 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.