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Science 8 December 1995:
Vol. 270. no. 5242, pp. 1667 - 1671
DOI: 10.1126/science.270.5242.1667
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Reports

Conserved Initiator Proteins in Eukaryotes

Kimberley A. Gavin,  Masumi Hidaka,  Bruce Stillman (1)

The origin recognition complex (ORC), a multisubunit protein identified in Saccharomyces cerevisiae, binds to chromosomal replicators and is required for the initiation of cellular DNA replication. Complementary DNAs (cDNAs) encoding proteins related to the two largest subunits of ORC were cloned from various eukaryotes. The cDNAs encoding proteins related to S. cerevisiae Orc1p were cloned from the budding yeast Kluyveromyces lactis, the fission yeast Schizosaccharomyces pombe,and human cells. These proteins show similarity to regulators of the S and M phases of the cell cycle. Genetic analysis of orc1+ from S. pombe reveals that it is essential for cell viability. The cDNAs encoding proteins related to S. cerevisiae Orc2p were cloned from Arabidopsis thaliana, Caenorhabditis elegans, and human cells. The human ORC-related proteins interact in vivo to form a complex. These studies suggest that ORC subunits are conserved and that the role of ORC is a general feature of eukaryotic DNA replication.


K. A. Gavin, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA, and Program in Genetics, State University of New York, Stony Brook, NY 11794, USA.
M. Hidaka and B. Stillman, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
(1) To whom correspondence should be addressed.


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The Orc4p and Orc5p Subunits of the Xenopus and Human Origin Recognition Complex Are Related to Orc1p and Cdc6p.
T. Tugal, X. H. Zou-Yang, K. Gavin, D. Pappin, B. Canas, R. Kobayashi, T. Hunt, and B. Stillman (1998)
J. Biol. Chem. 273, 32421-32429
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J. Virol. 72, 8559-8567
   Abstract »    Full Text »    PDF »
Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F.
G. Hateboer, A. Wobst, B. O. Petersen, L. Le Cam, E. Vigo, C. Sardet, and K. Helin (1998)
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   Abstract »    Full Text »
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W. V. Ng, S. A. Ciufo, T. M. Smith, R. E. Bumgarner, D. Baskin, J. Faust, B. Hall, C. Loretz, J. Seto, J. Slagel, et al. (1998)
Genome Res. 8, 1131-1141
   Abstract »    Full Text »
ORC5L, a New Member of the Human Origin Recognition Complex, Is Deleted in Uterine Leiomyomas and Malignant Myeloid Diseases.
D. G. Quintana, K. C. Thome, Z.-h. Hou, A. H. Ligon, C. C. Morton, and A. Dutta (1998)
J. Biol. Chem. 273, 27137-27145
   Abstract »    Full Text »    PDF »
Human Minichromosome Maintenance Proteins and Human Origin Recognition Complex 2 Protein on Chromatin.
M. Ritzi, M. Baack, C. Musahl, P. Romanowski, R. A. Laskey, and R. Knippers (1998)
J. Biol. Chem. 273, 24543-24549
   Abstract »    Full Text »    PDF »
Identification of a Novel 81-kDa Component of the Xenopus Origin Recognition Complex.
P. B. Carpenter and W. G. Dunphy (1998)
J. Biol. Chem. 273, 24891-24897
   Abstract »    Full Text »    PDF »
Growth Regulation of the Expression of Mouse cDNA and Gene Encoding a Serine/Threonine Kinase Related to Saccharomyces cerevisiae CDC7 Essential for G1/S Transition. STRUCTURE, CHROMOSOMAL LOCALIZATION, AND EXPRESSION OF MOUSE GENE FOR S. CEREVISIAE CDC7-RELATED KINASE.
J. M. Kim, N. Sato, M. Yamada, K.-i. Arai, and H. Masai (1998)
J. Biol. Chem. 273, 23248-23257
   Abstract »    Full Text »    PDF »
Identification of a Novel MCM3-associated Protein that Facilitates MCM3 Nuclear Localization.
Y. Takei and G. Tsujimoto (1998)
J. Biol. Chem. 273, 22177-22180
   Abstract »    Full Text »    PDF »
The Human Homolog of Saccharomyces cerevisiae CDC45.
P. Saha, K. C. Thome, R. Yamaguchi, Z.-h. Hou, S. Weremowicz, and A. Dutta (1998)
J. Biol. Chem. 273, 18205-18209
   Abstract »    Full Text »    PDF »
Human CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase.
P. Saha, J. Chen, K. C. Thome, S. J. Lawlis, Z.-h. Hou, M. Hendricks, J. D. Parvin, and A. Dutta (1998)
Mol. Cell. Biol. 18, 2758-2767
   Abstract »    Full Text »
Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
Z. Yan, J. DeGregori, R. Shohet, G. Leone, B. Stillman, J. R. Nevins, and R. S. Williams (1998)
PNAS 95, 3603-3608
   Abstract »    Full Text »    PDF »
Identification of a Preinitiation Step in DNA Replication That Is Independent of Origin Recognition Complex and cdc6, but Dependent on cdk2.
X. H. Hua and J. Newport (1998)
J. Cell Biol. 140, 271-281
   Abstract »    Full Text »    PDF »
Negative Regulation of Cdc18 DNA Replication Protein by Cdc2.
A. Lopez-Girona, O. Mondesert, J. Leatherwood, and P. Russell (1998)
Mol. Biol. Cell 9, 63-73
   Abstract »    Full Text »
Identification and characterization of a human protein kinase related to budding yeast Cdc7p.
W. Jiang and T. Hunter (1997)
PNAS 94, 14320-14325
   Abstract »    Full Text »    PDF »
Schizosaccharomyces pombe cdc20+ encodes DNA polymerase varepsilon  and is required for chromosomal replication but not for the S phase checkpoint.
G. D'Urso and P. Nurse (1997)
PNAS 94, 12491-12496
   Abstract »    Full Text »    PDF »
Identification of HsORC4, a Member of the Human Origin of Replication Recognition Complex.
D. G. Quintana, Z.-h. Hou, K. C. Thome, M. Hendricks, P. Saha, and A. Dutta (1997)
J. Biol. Chem. 272, 28247-28251
   Abstract »    Full Text »    PDF »
Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation.
P. V. Jallepalli, G. W. Brown, M. Muzi-Falconi, D. Tien, and T. J. Kelly (1997)
Genes & Dev. 11, 2767-2779
   Abstract »    Full Text »    PDF »
Interaction of the S phase regulator Cdc18 with cyclin-dependent kinase in fission yeast.
G. W. Brown, P. V. Jallepalli, B. J. Huneycutt, and T. J. Kelly (1997)
PNAS 94, 6142-6147
   Abstract »    Full Text »    PDF »
In Vivo Interaction of Human MCM Heterohexameric Complexes with Chromatin. POSSIBLE INVOLVEMENT OF ATP.
M. Fujita, T. Kiyono, Y. Hayashi, and M. Ishibashi (1997)
J. Biol. Chem. 272, 10928-10935
   Abstract »    Full Text »    PDF »
The k43 gene, required for chorion gene amplification and diploid cell chromosome replication, encodes the Drosophila homolog of yeast origin recognition complex subunit 2.
G. Landis, R. Kelley, A. C. Spradling, and J. Tower (1997)
PNAS 94, 3888-3892
   Abstract »    Full Text »    PDF »
A Role for Cdk2 Kinase in Negatively Regulating DNA Replication during S Phase of the Cell Cycle.
X. H. Hua, H. Yan, and J. Newport (1997)
J. Cell Biol. 137, 183-192
   Abstract »    Full Text »    PDF »
A human protein related to yeast Cdc6p.
R. S. Williams, R. V. Shohet, and B. Stillman (1997)
PNAS 94, 142-147
   Abstract »    Full Text »    PDF »
Disruption of Re-replication Control by Overexpression of Human ORC1 in Fission Yeast.
D. A. Wolf, D. Wu, and F. McKeon (1996)
J. Biol. Chem. 271, 32503-32506
   Abstract »    Full Text »    PDF »
Cell Cycle Control of DNA Replication.
B. Stillman (1996)
Science 274, 1659-1663
   Abstract »    Full Text »
Once and only once upon a time: specifying and regulating origins of DNA replication in eukaryotic cells..
J F Diffley (1996)
Genes & Dev. 10, 2819-2830
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The ORC1 homolog orp1 in fission yeast plays a key role in regulating onset of S phase..
B Grallert and P Nurse (1996)
Genes & Dev. 10, 2644-2654
   Abstract »    PDF »
Purification, Gene Cloning, and Reconstitution of the Heterotrimeric Single-stranded DNA-binding Protein from Schizosaccharomyces pombe.
M. Ishiai, J. P. Sanchez, A. A. Amin, Y. Murakami, and J. Hurwitz (1996)
J. Biol. Chem. 271, 20868-20878
   Abstract »    Full Text »    PDF »
Separation of Origin Recognition Complex Functions by Cross-Species Complementation.
A. E. Ehrenhofer-Murray, M. Gossen, D. T. S. Pak, M. R. Botchan, and J. Rine (1995)
Science 270, 1671-1674
   Abstract »    PDF »
Subsets of Human Origin Recognition Complex (ORC) Subunits Are Expressed in Non-proliferating Cells and Associate with Non-ORC Proteins.
K. C. Thome, S. K. Dhar, D. G. Quintana, L. Delmolino, A. Shahsafaei, and A. Dutta (2000)
J. Biol. Chem. 275, 35233-35241
   Abstract »    Full Text »    PDF »
Identification and Characterization of the Human ORC6 Homolog.
S. K. Dhar and A. Dutta (2000)
J. Biol. Chem. 275, 34983-34988
   Abstract »    Full Text »    PDF »
The Human Origin Recognition Complex Protein 1 Dissociates from Chromatin during S Phase in HeLa Cells.
S. Kreitz, M. Ritzi, M. Baack, and R. Knippers (2001)
J. Biol. Chem. 276, 6337-6342
   Abstract »    Full Text »    PDF »
Multiple Mechanisms Regulate Subcellular Localization of Human CDC6.
L. M. Delmolino, P. Saha, and A. Dutta (2001)
J. Biol. Chem. 276, 26947-26954
   Abstract »    Full Text »    PDF »
Assembly of the Human Origin Recognition Complex.
S. Vashee, P. Simancek, M. D. Challberg, and T. J. Kelly (2001)
J. Biol. Chem. 276, 26666-26673
   Abstract »    Full Text »    PDF »
Architecture of the Human Origin Recognition Complex.
S. K. Dhar, L. Delmolino, and A. Dutta (2001)
J. Biol. Chem. 276, 29067-29071
   Abstract »    Full Text »    PDF »
A Potential Role for Mini-chromosome Maintenance (MCM) Proteins in Initiation at the Dihydrofolate Reductase Replication Origin.
M. G. Alexandrow, M. Ritzi, A. Pemov, and J. L. Hamlin (2002)
J. Biol. Chem. 277, 2702-2708
   Abstract »    Full Text »    PDF »


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