ORC1 explained

Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene.^{[1] [2]} It is closely related to CDC6, and both are the same protein in archaea.^[3]

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 and
• CDC6,^[4]
• Cell division cycle 7-related protein kinase,
• Cyclin-dependent kinase 2,
• MCM2,
• MCM4,
• MCM6,
• MCM7,
• MYST2,^[5]
• ORC2,^{[6] [7] [8] [9]}
• ORC4,^[6]
• ORC5,^[6] and
• SKP2.^[9]

Further reading

• Gavin KA, Hidaka M, Stillman B . Conserved initiator proteins in eukaryotes . Science . 270 . 5242 . 1667–71 . Dec 1995 . 7502077 . 10.1126/science.270.5242.1667 . 1995Sci...270.1667G . 43633493 .
• Ohtani K, DeGregori J, Leone G, Herendeen DR, Kelly TJ, Nevins JR . 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 . Dec 1996 . 8943353 . 231701 . 10.1128/mcb.16.12.6977.
• Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A . 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 . May 1998 . 9566895 . 110655 . 10.1128/mcb.18.5.2758.
• Iizuka M, Stillman B . Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein . The Journal of Biological Chemistry . 274 . 33 . 23027–34 . Aug 1999 . 10438470 . 10.1074/jbc.274.33.23027 . free .
• Jiang W, McDonald D, Hope TJ, Hunter T . Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication . The EMBO Journal . 18 . 20 . 5703–13 . Oct 1999 . 10523313 . 1171637 . 10.1093/emboj/18.20.5703 .
• Tatsumi Y, Tsurimoto T, Shirahige K, Yoshikawa H, Obuse C . Association of human origin recognition complex 1 with chromatin DNA and nuclease-resistant nuclear structures . The Journal of Biological Chemistry . 275 . 8 . 5904–10 . Feb 2000 . 10681582 . 10.1074/jbc.275.8.5904 . free .
• Thome KC, Dhar SK, Quintana DG, Delmolino L, Shahsafaei A, Dutta A . 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 . Nov 2000 . 10954718 . 10.1074/jbc.M005765200 . free .
• Vashee S, Simancek P, Challberg MD, Kelly TJ . Assembly of the human origin recognition complex . The Journal of Biological Chemistry . 276 . 28 . 26666–73 . Jul 2001 . 11323433 . 10.1074/jbc.M102493200 . free .
• Laman H, Peters G, Jones N . Cyclin-mediated export of human Orc1 . Experimental Cell Research . 271 . 2 . 230–7 . Dec 2001 . 11716535 . 10.1006/excr.2001.5360 .
• Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T . Nuclear organization of DNA replication initiation proteins in mammalian cells . The Journal of Biological Chemistry . 277 . 12 . 10354–61 . Mar 2002 . 11779870 . 10.1074/jbc.M111398200 . free .
• Ladenburger EM, Keller C, Knippers R . 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 . Feb 2002 . 11809796 . 134626 . 10.1128/MCB.22.4.1036-1048.2002 .
• Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B . Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication . Molecular Cell . 9 . 3 . 481–91 . Mar 2002 . 11931757 . 10.1016/S1097-2765(02)00467-7 . free .
• Kneissl M, Pütter V, Szalay AA, Grummt F . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . Journal of Molecular Biology . 327 . 1 . 111–28 . Mar 2003 . 12614612 . 10.1016/S0022-2836(03)00079-2 .
• Ohta S, Tatsumi Y, Fujita M, Tsurimoto T, Obuse C . 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 . Oct 2003 . 12909626 . 10.1074/jbc.M307535200 . free .
• Tatsumi Y, Ohta S, Kimura H, Tsurimoto T, Obuse C . The ORC1 cycle in human cells: I. cell cycle-regulated oscillation of human ORC1 . The Journal of Biological Chemistry . 278 . 42 . 41528–34 . Oct 2003 . 12909627 . 10.1074/jbc.M307534200 . free.
• Abdurashidova G, Danailov MB, Ochem A, Triolo G, Djeliova V, Radulescu S, Vindigni A, Riva S, Falaschi A . Localization of proteins bound to a replication origin of human DNA along the cell cycle . The EMBO Journal . 22 . 16 . 4294–303 . Aug 2003 . 12912926 . 175794 . 10.1093/emboj/cdg404 .
• Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J . Self-assembling protein microarrays . Science . 305 . 5680 . 86–90 . Jul 2004 . 15232106 . 10.1126/science.1097639 . 2004Sci...305...86R . 20936301 .
• Lidonnici MR, Rossi R, Paixão S, Mendoza-Maldonado R, Paolinelli R, Arcangeli C, Giacca M, Biamonti G, Montecucco A . 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 . Oct 2004 . 15454574 . 10.1242/jcs.01405 . free .

Notes and References

1. Eki T, Okumura K, Amin A, Ishiai M, Abe M, Nogami M, Taguchi H, Hurwitz J, Murakami Y, Hanaoka F . Mapping of the human homologue (ORC1L) of the yeast origin recognition complex subunit 1 gene to chromosome band 1p32 . Genomics . 36 . 3 . 559–61 . Sep 1996 . 8884289 . 10.1006/geno.1996.0511 .
2. Web site: Entrez Gene: ORC1L origin recognition complex, subunit 1-like (yeast).
3. Ausiannikava . Darya . Allers . Thorsten . Diversity of DNA Replication in the Archaea . Genes . 31 January 2017 . 8 . 2 . 56 . 10.3390/genes8020056 . 28146124 . 5333045. free .
4. Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A . 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 . May 1998 . 9566895 . 110655 . 10.1128/mcb.18.5.2758.
5. Iizuka M, Stillman B . Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein . The Journal of Biological Chemistry . 274 . 33 . 23027–34 . Aug 1999 . 10438470 . 10.1074/jbc.274.33.23027. free .
6. Kneissl M, Pütter V, Szalay AA, Grummt F . Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells . Journal of Molecular Biology . 327 . 1 . 111–28 . Mar 2003 . 12614612 . 10.1016/s0022-2836(03)00079-2.
7. Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T . Nuclear organization of DNA replication initiation proteins in mammalian cells . The Journal of Biological Chemistry . 277 . 12 . 10354–61 . Mar 2002 . 11779870 . 10.1074/jbc.M111398200 . free .
8. Vashee S, Simancek P, Challberg MD, Kelly TJ . Assembly of the human origin recognition complex . The Journal of Biological Chemistry . 276 . 28 . 26666–73 . Jul 2001 . 11323433 . 10.1074/jbc.M102493200 . free .
9. Méndez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B . Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication . Molecular Cell . 9 . 3 . 481–91 . Mar 2002 . 11931757 . 10.1016/s1097-2765(02)00467-7. free .