Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Genome-Wide Distribution of ORC and MCM Proteins in S. cerevisiae: High-Resolution Mapping of Replication Origins
John J. Wyrick,12*Jennifer G. Aparicio,3*Ting Chen,3John D. Barnett,2Ezra G. Jennings,12Richard A. Young,12Stephen P. Bell,14Oscar M. Aparicio3
DNA replication origins are fundamental to chromosome
organization and duplication, but understanding of these elements islimited because only a small fraction of these sites have beenidentified in eukaryotic genomes. Origin Recognition Complex (ORC)and
minichromosome maintenance (MCM) proteins form prereplicativecomplexes
at origins of replication. Using these proteins as molecularlandmarks
for origins, we identified ORC- and MCM-bound sitesthroughout the
yeast genome. Four hundred twenty-nine sites inthe yeast genome were
predicted to contain replication origins,and ~80% of the loci
identified on chromosome X demonstrated originfunction. A substantial
fraction of the predicted origins areassociated with repetitive DNA
sequences, including subtelomericelements (X and Y') and
transposable element-associated sequences(long terminal repeats).
These findings identify the global setof yeast replication origins and
open avenues of investigationinto the role(s) ORC and MCM proteins
play in chromosomal architectureand dynamics.
1 Department of Biology, Massachusetts
Institute of Technology, Cambridge, MA 02139, USA.
2 Whitehead Institute for Biomedical Research,
Cambridge, MA 02142, USA.
3 Program in Molecular and
Computational Biology, University of Southern California, Los Angeles,
CA 90089-1340, USA.
4 Howard Hughes Medical
Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
*
These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail:
oaparici{at}usc.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Bruce Stillman (14 December 2001) Science294 (5550), 2301.
[DOI: 10.1126/science.1067929] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Differential association of Orc1 and Sir2 proteins to telomeric domains in Plasmodium falciparum.
L. Mancio-Silva, A. P. Rojas-Meza, M. Vargas, A. Scherf, and R. Hernandez-Rivas (2008)
J. Cell Sci.
121, 2046-2053
|Abstract »|Full Text »|PDF »
Controlled exchange of chromosomal arms reveals principles driving telomere interactions in yeast.
H. Schober, V. Kalck, M. A. Vega-Palas, G. Van Houwe, D. Sage, M. Unser, M. R. Gartenberg, and S. M. Gasser (2008)
Genome Res.
18, 261-271
|Abstract »|Full Text »|PDF »
Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase.
T. M. Roberts, I. W. Zaidi, J. A. Vaisica, M. Peter, and G. W. Brown (2008)
Mol. Biol. Cell
19, 171-180
|Abstract »|Full Text »|PDF »
Subtelomeric Elements Influence But Do Not Determine Silencing Levels at Saccharomyces cerevisiae Telomeres.
Identification of Mutations That Decrease the Stability of a Fragment of Saccharomyces cerevisiae Chromosome III Lacking Efficient Replicators.
J. F. Theis, A. Dershowitz, C. Irene, C. Maciariello, M. L. Tobin, G. Liberi, S. Tabrizifard, M. Korus, L. Fabiani, and C. S. Newlon (2007)
Genetics
177, 1445-1458
|Abstract »|Full Text »|PDF »
Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation.
R. Bermejo, Y. Doksani, T. Capra, Y.-M. Katou, H. Tanaka, K. Shirahige, and M. Foiani (2007)
Genes & Dev.
21, 1921-1936
|Abstract »|Full Text »|PDF »
Linear Derivatives of Saccharomyces cerevisiae Chromosome III Can Be Maintained in the Absence of Autonomously Replicating Sequence Elements.
A. Dershowitz, M. Snyder, M. Sbia, J. H. Skurnick, L. Y. Ong, and C. S. Newlon (2007)
Mol. Cell. Biol.
27, 4652-4663
|Abstract »|Full Text »|PDF »
Genomewide and biochemical analyses of DNA-binding activity of Cdc6/Orc1 and Mcm proteins in Pyrococcus sp..
F. Matsunaga, A. Glatigny, M.-H. Mucchielli-Giorgi, N. Agier, H. Delacroix, L. Marisa, P. Durosay, Y. Ishino, L. Aggerbeck, and P. Forterre (2007)
Nucleic Acids Res.
35, 3214-3222
|Abstract »|Full Text »|PDF »
In vitro analysis of DNA-protein interactions by proximity ligation.
S. M. Gustafsdottir, J. Schlingemann, A. Rada-Iglesias, E. Schallmeiner, M. Kamali-Moghaddam, C. Wadelius, and U. Landegren (2007)
PNAS
104, 3067-3072
|Abstract »|Full Text »|PDF »
OriDB: a DNA replication origin database.
C. A. Nieduszynski, S.-i. Hiraga, P. Ak, C. J. Benham, and A. D. Donaldson (2007)
Nucleic Acids Res.
35, D40-D46
|Abstract »|Full Text »|PDF »
Using genomics and proteomics to investigate mechanisms of transcriptional silencing in Saccharomyces cerevisiae.
Palm Mutants in DNA Polymerases {alpha} and {eta} Alter DNA Replication Fidelity and Translesion Activity.
A. Niimi, S. Limsirichaikul, S. Yoshida, S. Iwai, C. Masutani, F. Hanaoka, E. T. Kool, Y. Nishiyama, and M. Suzuki (2004)
Mol. Cell. Biol.
24, 2734-2746
|Abstract »|Full Text »|PDF »
Telomere Repeat Binding Factors TRF1, TRF2, and hRAP1 Modulate Replication of Epstein-Barr Virus OriP.
Z. Deng, C. Atanasiu, J. S. Burg, D. Broccoli, and P. M. Lieberman (2003)
J. Virol.
77, 11992-12001
|Abstract »|Full Text »|PDF »
Genetic and Biochemical Evaluation of the Importance of Cdc6 in Regulating Mitotic Exit.
V. Archambault, C. X. Li, A. J. Tackett, R. Wasch, B. T. Chait, M. P. Rout, and F. R. Cross (2003)
Mol. Biol. Cell
14, 4592-4604
|Abstract »|Full Text »|PDF »
CpG Methylation of DNA Restricts Prereplication Complex Assembly in Xenopus Egg Extracts.
Evidence for a Role of MCM (Mini-chromosome Maintenance)5 in Transcriptional Repression of Sub-telomeric and Ty-proximal Genes in Saccharomyces cerevisiae.
R. Dziak, D. Leishman, M. Radovic, B. K. Tye, and K. Yankulov (2003)
J. Biol. Chem.
278, 27372-27381
|Abstract »|Full Text »|PDF »
A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells.
Z. Li, S. Van Calcar, C. Qu, W. K. Cavenee, M. Q. Zhang, and B. Ren (2003)
PNAS
100, 8164-8169
|Abstract »|Full Text »|PDF »
Mcm7, a Subunit of the Presumptive MCM Helicase, Modulates Its Own Expression in Conjunction with Mcm1.
M. J. Fitch, J. J. Donato, and B. K. Tye (2003)
J. Biol. Chem.
278, 25408-25416
|Abstract »|Full Text »|PDF »
Drosophila Mcm10 Interacts with Members of the Prereplication Complex and Is Required for Proper Chromosome Condensation.
V. K. Chang, M. J. Fitch, J. J. Donato, T. W. Christensen, A. M. Merchant, and B. K. Tye (2003)
J. Biol. Chem.
278, 6093-6100
|Abstract »|Full Text »|PDF »
The Dihydrofolate Reductase Origin of Replication Does Not Contain Any Nonredundant Genetic Elements Required for Origin Activity.
L. D. Mesner, X. Li, P. A. Dijkwel, and J. L. Hamlin (2003)
Mol. Cell. Biol.
23, 804-814
|Abstract »|Full Text »
Targeted Nucleotide Repair of cyc1 Mutations in Saccharomyces cerevisiae Directed by Modified Single-Stranded DNA Oligonucleotides.
Genetic Diversity in Yeast Assessed With Whole-Genome Oligonucleotide Arrays.
E. A. Winzeler, C. I. Castillo-Davis, G. Oshiro, D. Liang, D. R. Richards, Y. Zhou, and D. L. Hartl (2003)
Genetics
163, 79-89
|Abstract »|Full Text »|PDF »
Transcriptional Regulatory Networks in Saccharomyces cerevisiae.
T. I. Lee, N. J. Rinaldi, F. Robert, D. T. Odom, Z. Bar-Joseph, G. K. Gerber, N. M. Hannett, C. T. Harbison, C. M. Thompson, I. Simon, et al. (2002)
Science
298, 799-804
|Abstract »|Full Text »|PDF »
Human Mcm proteins at a replication origin during the G1 to S phase transition.
D. Schaarschmidt, E.-M. Ladenburger, C. Keller, and R. Knippers (2002)
Nucleic Acids Res.
30, 4176-4185
|Abstract »|Full Text »|PDF »
To fire or not to fire: origin activation in Saccharomyces cerevisiae ribosomal DNA.
A. S. Ivessa and V. A. Zakian (2002)
Genes & Dev.
16, 2459-2464
|Full Text »|PDF »
Ku complex controls the replication time of DNA in telomere regions.
A. J. Cosgrove, C. A. Nieduszynski, and A. D. Donaldson (2002)
Genes & Dev.
16, 2485-2490
|Abstract »|Full Text »|PDF »
The Origin Recognition Complex Marks a Replication Origin in the Human TOP1 Gene Promoter.
C. Keller, E.-M. Ladenburger, M. Kremer, and R. Knippers (2002)
J. Biol. Chem.
277, 31430-31440
|Abstract »|Full Text »|PDF »
Preformed hexamers of SV40 T antigen are active in RNA and origin-DNA unwinding.
H. Uhlmann-Schiffler, S. Seinsoth, and H. Stahl (2002)
Nucleic Acids Res.
30, 3192-3201
|Abstract »|Full Text »|PDF »
Replicational organization of three weakly expressed loci in Physarum polycephalum.
C. Maric, E. Swanston, J. Bailey, and G. Pierron (2002)
Nucleic Acids Res.
30, 2261-2269
|Abstract »|Full Text »|PDF »
Genome-wide location and regulated recruitment of the RSC nucleosome-remodeling complex.
H. H. Ng, F. Robert, R. A. Young, and K. Struhl (2002)
Genes & Dev.
16, 806-819
|Abstract »|Full Text »|PDF »
The origin recognition complex: from simple origins to complex functions.