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Science 17 December 1993:
Vol. 262. no. 5141, pp. 1870 - 1874
DOI: 10.1126/science.8266075
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Articles

Science, Vol 262, Issue 5141, 1870-1874
Copyright © 1993 by American Association for the Advancement of Science

articles

Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system

JJ Li and I Herskowitz

Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.

Here a method is described to identify genes encoding proteins that recognize a specific DNA sequence. A bank of random protein segments tagged with a transcriptional activation domain is screened for proteins that can activate a reporter gene containing the sequence in its promoter. This strategy was used to identify an essential protein that interacts in vivo with the yeast origin of DNA replication. Matches between its predicted amino acid sequence and peptide sequence obtained from the 50-kilodalton subunit of the yeast origin recognition complex (ORC) established that the gene isolated here, ORC6, encodes this subunit. These observations provide evidence that ORC recognizes yeast replication origins in vivo.


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Unraveling transcription regulatory networks by protein-DNA and protein-protein interaction mapping.
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Regulation of Sexual Dimorphism: Mutational and Chemogenetic Analysis of the Doublesex DM Domain.
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PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets.
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Decreased origin usage and initiation of DNA replication in haploinsufficient HCT116 Ku80+/- cells.
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cis-Regulatory Elements for Mesophyll-Specific Gene Expression in the C4 Plant Flaveria trinervia, the Promoter of the C4 Phosphoenolpyruvate Carboxylase Gene.
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The ORC1 Cycle in Human Cells: I. CELL CYCLE-REGULATED OSCILLATION OF HUMAN ORC1.
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Arabidopsis ABI5 Subfamily Members Have Distinct DNA-Binding and Transcriptional Activities.
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Plant Physiology 130, 688-697
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Plant Cell Physiol. 43, 1006-1016
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A Kruppel-Associated Box-Zinc Finger Protein, NT2, Represses Cell-Type-Specific Promoter Activity of the {alpha}2(XI) Collagen Gene.
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Mol. Cell. Biol. 22, 4256-4267
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The origin recognition complex: from simple origins to complex functions.
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Genes & Dev. 16, 659-672
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Identification of a Multifunctional Domain in Autonomously Replicating Sequence-Binding Factor 1 Required for Transcriptional Activation, DNA Replication, and Gene Silencing.
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Chromosome Dynamics in the Yeast Interphase Nucleus.
P. Heun, T. Laroche, K. Shimada, P. Furrer, and S. M. Gasser (2001)
Science 294, 2181-2186
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The Schizosaccharomyces pombe origin recognition complex interacts with multiple AT-rich regions of the replication origin DNA by means of the AT-hook domains of the spOrc4 protein.
J.-K. Lee, K.-Y. Moon, Y. Jiang, and J. Hurwitz (2001)
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Differential Modulation of Transcriptional Activity of Estrogen Receptors by Direct Protein-Protein Interactions with the T Cell Factor Family of Transcription Factors.
M. El-Tanani, D. G. Fernig, R. Barraclough, C. Green, and P. Rudland (2001)
J. Biol. Chem. 276, 41675-41682
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Metastasis-inducing DNA Regulates the Expression of the Osteopontin Gene by Binding the Transcription Factor Tcf-4.
M. El-Tanani, R. Barraclough, M. C. Wilkinson, and P. S. Rudland (2001)
Cancer Res. 61, 5619-5629
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Saccharomyces cerevisiae CTF18 and CTF4 Are Required for Sister Chromatid Cohesion.
J. S. Hanna, E. S. Kroll, V. Lundblad, and F. A. Spencer (2001)
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Interaction of Xenopus Cdc2{middle dot}Cyclin A1 with the Origin Recognition Complex.
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Nucleic Acids Res. 28, 570-581
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Identification of COUP-TF as a Transcriptional Repressor of the c-mos Proto-oncogene.
H.-b. Lin, M. Jurk, T. Gulick, and G. M. Cooper (1999)
J. Biol. Chem. 274, 36796-36800
   Abstract »    Full Text »    PDF »
A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene.
K. Yamada, H. Ogawa, S.-i. Honda, N. Harada, and T. Okazaki (1999)
J. Biol. Chem. 274, 32279-32286
   Abstract »    Full Text »    PDF »
Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily.
V. L. Gerlach, L. Aravind, G. Gotway, R. A. Schultz, E. V. Koonin, and E. C. Friedberg (1999)
PNAS 96, 11922-11927
   Abstract »    Full Text »    PDF »
The Cdc6 Nucleotide-Binding Site Regulates Its Activity in DNA Replication in Human Cells.
U. Herbig, C. A. Marlar, and E. Fanning (1999)
Mol. Biol. Cell 10, 2631-2645
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Subclass-specific Nuclear Localization of a Novel CD4 Silencer Binding Factor.
W. W.S. Kim and G. Siu (1999)
J. Exp. Med. 190, 281-292
   Abstract »    Full Text »    PDF »
A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore.
J. Ortiz, O. Stemmann, S. Rank, and J. Lechner (1999)
Genes & Dev. 13, 1140-1155
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The Essential Role of Saccharomyces cerevisiae CDC6 Nucleotide-binding Site in Cell Growth, DNA Synthesis, and Orc1 Association.
B. Wang, L. Feng, Y. Hu, S. H. Huang, C. P. Reynolds, L. Wu, and A. Y. Jong (1999)
J. Biol. Chem. 274, 8291-8298
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The fission yeast homologue of Orc4p binds to replication origin DNA via multiple AT-hooks.
R.-Y. Chuang and T. J. Kelly (1999)
PNAS 96, 2656-2661
   Abstract »    Full Text »    PDF »
Cyclin B-Cdk1 Kinase Stimulates ORC- and Cdc6-Independent Steps of Semiconservative Plasmid Replication in Yeast Nuclear Extracts.
B. P. Duncker, P. Pasero, D. Braguglia, P. Heun, M. Weinreich, and S. M. Gasser (1999)
Mol. Cell. Biol. 19, 1226-1241
   Abstract »    Full Text »    PDF »
Role for a YY1-Binding Element in Replication-Dependent Mouse Histone Gene Expression.
K. A. Eliassen, A. Baldwin, E. M. Sikorski, and M. M. Hurt (1998)
Mol. Cell. Biol. 18, 7106-7118
   Abstract »    Full Text »
The Yeast Protein Complex Containing Cdc68 and Pob3 Mediates Core-Promoter Repression Through the Cdc68 N-Terminal Domain.
D. R. H. Evans, N. K. Brewster, Q. Xu, A. Rowley, B. A. Altheim, G. C. Johnston, and R. A. Singer (1998)
Genetics 150, 1393-1405
   Abstract »    Full Text »
Cloning and Characterization of a Novel Human Hepatocyte Transcription Factor, hB1F, Which Binds and Activates Enhancer II of Hepatitis B Virus.
M. Li, Y.-H. Xie, Y.-Y. Kong, X. Wu, L. Zhu, and Y. Wang (1998)
J. Biol. Chem. 273, 29022-29031
   Abstract »    Full Text »    PDF »
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 »
A Novel Function of the DNA Repair Gene rhp6 in Mating-Type Silencing by Chromatin Remodeling in Fission Yeast.
J. Singh, V. Goel, and A. J. S. Klar (1998)
Mol. Cell. Biol. 18, 5511-5522
   Abstract »    Full Text »
Sir Proteins, Rif Proteins, and Cdc13p Bind Saccharomyces Telomeres In Vivo.
B. D. Bourns, M. K. Alexander, A. M. Smith, and V. A. Zakian (1998)
Mol. Cell. Biol. 18, 5600-5608
   Abstract »    Full Text »
Mutational Effect of Fission Yeast Polalpha on Cell Cycle Events.
D. Bhaumik and T. S.-F. Wang (1998)
Mol. Biol. Cell 9, 2107-2123
   Abstract »    Full Text »
Role of the CLOCK Protein in the Mammalian Circadian Mechanism.
N. Gekakis, D. Staknis, H. B. Nguyen, F. C. Davis, L. D. Wilsbacher, D. P. King, J. S. Takahashi, and C. J. Weitz (1998)
Science 280, 1564-1569
   Abstract »    Full Text »
Closing the Circadian Loop: CLOCK-Induced Transcription of Its Own Inhibitors per and tim.
T. K. Darlington, K. Wager-Smith, M. F. Ceriani, D. Staknis, N. Gekakis, T. D. Steeves, C. J. Weitz, J. S. Takahashi, and S. A. Kay (1998)
Science 280, 1599-1603
   Abstract »    Full Text »
The HOXC11 Homeodomain Protein Interacts with the Lactase-Phlorizin Hydrolase Promoter and Stimulates HNF1alpha -dependent Transcription.
C. Mitchelmore, J. T. Troelsen, H. Sjostrom, and O. Noren (1998)
J. Biol. Chem. 273, 13297-13306
   Abstract »    Full Text »    PDF »
Biochemical Function of Mouse Minichromosome Maintenance 2 Protein.
Y. Ishimi, Y. Komamura, Z. You, and H. Kimura (1998)
J. Biol. Chem. 273, 8369-8375
   Abstract »    Full Text »    PDF »
Conversion of the omega  subunit of Escherichia coli RNA polymerase into a transcriptional activator or an activation target.
S. L. Dove and A. Hochschild (1998)
Genes & Dev. 12, 745-754
   Abstract »    Full Text »
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 »
Saccharomyces cerevisiae Cdc6 Stimulates Abf1 DNA Binding Activity.
L. Feng, B. Wang, and A. Jong (1998)
J. Biol. Chem. 273, 1298-1302
   Abstract »    Full Text »    PDF »
A Novel ets-related Transcription Factor, ERT/ESX/ESE-1, Regulates Expression of the Transforming Growth Factor-beta Type II Receptor.
S.-G. Choi, Y. Yi, Y.-S. Kim, M. Kato, J. Chang, H.-W. Chung, K.-B. Hahm, H.-K. Yang, H. H. Rhee, Y.-J. Bang, et al. (1998)
J. Biol. Chem. 273, 110-117
   Abstract »    Full Text »    PDF »
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 »
Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast.
A. M. Stathopoulos and M. S. Cyert (1997)
Genes & Dev. 11, 3432-3444
   Abstract »    Full Text »    PDF »
A yeast genetic system for selecting small molecule inhibitors of protein-protein interactions in nanodroplets.
J. Huang and S. L. Schreiber (1997)
PNAS 94, 13396-13401
   Abstract »    Full Text »    PDF »
Selection of peptides that functionally replace a zinc finger in the Sp1 transcription factor by using a yeast combinatorial library.
X. Cheng, J. L. Boyer, and R. L. Juliano (1997)
PNAS 94, 14120-14125
   Abstract »    Full Text »    PDF »
CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication.
J. C. Owens, C. S. Detweiler, and J. J. Li (1997)
PNAS 94, 12521-12526
   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 »
A DNA Helicase Activity Is Associated with an MCM4, -6, and -7 Protein Complex.
Y. Ishimi (1997)
J. Biol. Chem. 272, 24508-24513
   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 »
Cloning and Characterization of a Transcription Factor That Binds to the Proximal Promoters of the Two Mouse Type I Collagen Genes.
T. Hasegawa, A. Takeuchi, O. Miyaishi, K.-i. Isobe, and B. de Crombrugghe (1997)
J. Biol. Chem. 272, 4915-4923
   Abstract »    Full Text »    PDF »
Arabidopsis thaliana CBF1 encodes an AP2 domain-containing transcriptional activator that binds to the C-repeat/DRE, a cis-acting DNA regulatory element that stimulates transcription in response to low temperature and water deficit.
E. J. Stockinger, S. J. Gilmour, and M. F. Thomashow (1997)
PNAS 94, 1035-1040
   Abstract »    Full Text »    PDF »
Cdc6p establishes and maintains a state of replication competence during G1 phase.
C. Detweiler and J. Li (1997)
J. Cell Sci. 110, 753-763
   Abstract »    PDF »
A critical arginine residue mediates cooperativity in the contact interface between transcription factors NFAT and AP-1.
B. R. Peterson, L. J. Sun, and G. L. Verdine (1996)
PNAS 93, 13671-13676
   Abstract »    Full Text »    PDF »
The bZIP Transcription Factor Nrl Stimulates Rhodopsin Promoter Activity in Primary Retinal Cell Cultures.
R. Kumar, S. Chen, D. Scheurer, Q.-L. Wang, E. Duh, C.-H. Sung, A. Rehemtulla, A. Swaroop, R. Adler, and D. J. Zack (1996)
J. Biol. Chem. 271, 29612-29618
   Abstract »    Full Text »    PDF »
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
   PDF »
Binding of Human Minichromosome Maintenance Proteins with Histone H3.
Y. Ishimi, S. Ichinose, A. Omori, K. Sato, and H. Kimura (1996)
J. Biol. Chem. 271, 24115-24122
   Abstract »    Full Text »    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 »
Conserved Initiator Proteins in Eukaryotes.
K. A. Gavin, M. Hidaka, and B. Stillman (1995)
Science 270, 1667-1671
   Abstract »    PDF »
A Drosophila Homolog of the Yeast Origin Recognition Complex.
M. Gossen, D. T. S. Pak, S. K. Hansen, J. K. Acharya, and M. R. Botchan (1995)
Science 270, 1674-1677
   Abstract »    PDF »
Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant..
J E Treisman, P J Follette, P H O'Farrell, and G M Rubin (1995)
Genes & Dev. 9, 1709-1715
   Abstract »    PDF »
The origin recognition complex has essential functions in transcriptional silencing and chromosomal replication..
C A Fox, S Loo, A Dillin, and J Rine (1995)
Genes & Dev. 9, 911-924
   Abstract »    PDF »
A murine replication protein accumulates temporarily in the heterochromatic regions of nuclei prior to initiation of DNA replication.
M Starborg, E Brundell, K Gell, C Larsson, I White, B Daneholt, and C Hoog (1995)
J. Cell Sci. 108, 927-934
   Abstract »    PDF »
Interaction of Dbf4, the Cdc7 protein kinase regulatory subunit, with yeast replication origins in vivo.
S. Dowell, P Romanowski, and J. Diffley (1994)
Science 265, 1243-1246
   Abstract »    PDF »
Two jobs for the origin replication complex.
C. Newlon (1993)
Science 262, 1830-1831
   PDF »
Yeast origin recognition complex functions in transcription silencing and DNA replication.
S. Bell, R Kobayashi, and B Stillman (1993)
Science 262, 1844-1849
   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 »
A Functional Comparison of BRCA1 C-terminal Domains in Transcription Activation and Chromatin Remodeling.
T. Miyake, Y.-F. Hu, D. S. Yu, and R. Li (2000)
J. Biol. Chem. 275, 40169-40173
   Abstract »    Full Text »    PDF »
Identification of Transcriptional Enhancer Factor-4 as a Transcriptional Modulator of CTP:Phosphocholine Cytidylyltransferase alpha.
H. Sugimoto, M. Bakovic, S. Yamashita, and D. E. Vance (2001)
J. Biol. Chem. 276, 12338-12344
   Abstract »    Full Text »    PDF »
Bipartite Binding of a Kinase Activator Activates Cdc7-related Kinase Essential for S Phase.
K. Ogino, T. Takeda, E. Matsui, H. Iiyama, C. Taniyama, K.-i. Arai, and H. Masai (2001)
J. Biol. Chem. 276, 31376-31387
   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 »
Synthetic promoter elements obtained by nucleotide sequence variation and selection for activity.
G. M. Edelman, R. Meech, G. C. Owens, and F. S. Jones (2000)
PNAS 97, 3038-3043
   Abstract »    Full Text »    PDF »
Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma.
C. J. DaFonseca, F. Shu, and J. J. Zhang (2001)
PNAS 98, 3034-3039
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LXRalpha functions as a cAMP-responsive transcriptional regulator of gene expression.
K. Tamura, Y. E. Chen, M. Horiuchi, Q. Chen, L. Daviet, Z. Yang, L. Daviet, M. Lopez-Ilasaca, H. Mu, R. E. Pratt, et al. (2000)
PNAS 97, 8513-8518
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Functional analysis of mutant and wild-type Drosophila origin recognition complex.
I. Chesnokov, D. Remus, and M. Botchan (2001)
PNAS 98, 11997-12002
   Abstract »    Full Text »    PDF »
Regulation of cyclic peptide biosynthesis in a plant pathogenic fungus by a novel transcription factor.
K. F. Pedley and J. D. Walton (2001)
PNAS 98, 14174-14179
   Abstract »    Full Text »    PDF »