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.


Science 6 June 1997:
Vol. 276. no. 5318, pp. 1547 - 1551
DOI: 10.1126/science.276.5318.1547

Reports

The Origin Recognition Complex, SIR1, and the S Phase Requirement for Silencing

Catherine A. Fox, * Ann E. Ehrenhofer-Murray, Stephen Loo, Jasper Rine dagger

Silencing of transcription in Saccharomyces cerevisiae has several links to DNA replication, including a role for the origin recognition complex (ORC), the DNA replication initiator, in both processes. In addition, the establishment of silencing at the HML and HMR loci requires cells to pass through the S phase of the cell cycle. Passage through S phase was required for silencing of HMR even under conditions in which ORC itself was no longer required. The requirement for ORC in silencing of HMR could be bypassed by tethering the Sir1 protein to the HMR-E silencer. However, ORC had a Sir1-independent role in transcriptional silencing at telomeres. Thus, the role of ORC in silencing was separable from its role in initiation, and the role of S phase in silencing was independent of replication initiation at the silencers.

Department of Molecular and Cell Biology, Division of Genetics, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
*   Present address: Department of Biomolecular Chemistry, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.

dagger    To whom correspondence should be addressed. E-mail: jasper{at}mendel.berkeley.edu


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Elaboration, Diversification and Regulation of the Sir1 Family of Silencing Proteins in Saccharomyces.
J. E. G. Gallagher, J. E. Babiarz, L. Teytelman, K. H. Wolfe, and J. Rine (2009)
Genetics 181, 1477-1491
   Abstract »    Full Text »    PDF »
Phylogenetic Conservation and Homology Modeling Help Reveal a Novel Domain within the Budding Yeast Heterochromatin Protein Sir1.
Z. Hou, J. R. Danzer, L. Mendoza, M. E. Bose, U. Muller, B. Williams, and C. A. Fox (2009)
Mol. Cell. Biol. 29, 687-702
   Abstract »    Full Text »    PDF »
Mcm10 Mediates the Interaction Between DNA Replication and Silencing Machineries.
I. Liachko and B. K. Tye (2009)
Genetics 181, 379-391
   Abstract »    Full Text »    PDF »
A Silencer Promotes the Assembly of Silenced Chromatin Independently of Recruitment.
P. J. Lynch and L. N. Rusche (2009)
Mol. Cell. Biol. 29, 43-56
   Abstract »    Full Text »    PDF »
Subtelomeric ACS-containing Proto-silencers Act as Antisilencers in Replication Factors Mutants in Saccharomyces cerevisiae.
M. A. Rehman, D. Wang, G. Fourel, E. Gilson, and K. Yankulov (2009)
Mol. Biol. Cell 20, 631-641
   Abstract »    Full Text »    PDF »
HST3/HST4-dependent Deacetylation of Lysine 56 of Histone H3 in Silent Chromatin.
B. Yang, A. Miller, and A. L. Kirchmaier (2008)
Mol. Biol. Cell 19, 4993-5005
   Abstract »    Full Text »    PDF »
Proliferating Cell Nuclear Antigen and ASF1 Modulate Silent Chromatin in Saccharomyces cerevisiae via Lysine 56 on Histone H3.
A. Miller, B. Yang, T. Foster, and A. L. Kirchmaier (2008)
Genetics 179, 793-809
   Abstract »    Full Text »    PDF »
Conversion of a Replication Origin to a Silencer through a Pathway Shared by a Forkhead Transcription Factor and an S Phase Cyclin.
L. Casey, E. E. Patterson, U. Muller, and C. A. Fox (2008)
Mol. Biol. Cell 19, 608-622
   Abstract »    Full Text »    PDF »
Differential Requirement of DNA Replication Factors for Subtelomeric ARS Consensus Sequence Protosilencers in Saccharomyces cerevisiae.
M. A. Rehman, G. Fourel, A. Mathews, D. Ramdin, M. Espinosa, E. Gilson, and K. Yankulov (2006)
Genetics 174, 1801-1810
   Abstract »    Full Text »    PDF »
New Alleles of SIR2 Define Cell-Cycle-Specific Silencing Functions.
M. Matecic, K. Martins-Taylor, M. Hickman, J. Tanny, D. Moazed, and S. G. Holmes (2006)
Genetics 173, 1939-1950
   Abstract »    Full Text »    PDF »
Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae.
D. G. Gibson, S. P. Bell, and O. M. Aparicio (2006)
Genes Cells 11, 557-573
   Abstract »    Full Text »    PDF »
Cell Cycle Requirements in Assembling Silent Chromatin in Saccharomyces cerevisiae.
A. L. Kirchmaier and J. Rine (2006)
Mol. Cell. Biol. 26, 852-862
   Abstract »    Full Text »    PDF »
Analyses of SUM1-1-Mediated Long-Range Repression.
L. Valenzuela, S. Gangadharan, and R. T. Kamakaka (2006)
Genetics 172, 99-112
   Abstract »    Full Text »    PDF »
ROR1/RPA2A, a Putative Replication Protein A2, Functions in Epigenetic Gene Silencing and in Regulation of Meristem Development in Arabidopsis.
R. Xia, J. Wang, C. Liu, Y. Wang, Y. Wang, J. Zhai, J. Liu, X. Hong, X. Cao, J.-K. Zhu, et al. (2006)
PLANT CELL 18, 85-103
   Abstract »    Full Text »    PDF »
The genes encoding Arabidopsis ORC subunits are E2F targets and the two ORC1 genes are differently expressed in proliferating and endoreplicating cells.
S. Diaz-Trivino, M. del Mar Castellano, M. de la Paz Sanchez, E. Ramirez-Parra, B. Desvoyes, and C. Gutierrez (2005)
Nucleic Acids Res. 33, 5404-5414
   Abstract »    Full Text »    PDF »
Mutations in the Nucleosome Core Enhance Transcriptional Silencing.
E. Y. Xu, X. Bi, M. J. Holland, D. E. Gottschling, and J. R. Broach (2005)
Mol. Cell. Biol. 25, 1846-1859
   Abstract »    Full Text »    PDF »
Dependence of ORC Silencing Function on NatA-Mediated N{alpha} Acetylation in Saccharomyces cerevisiae.
A. Geissenhoner, C. Weise, and A. E. Ehrenhofer-Murray (2004)
Mol. Cell. Biol. 24, 10300-10312
   Abstract »    Full Text »    PDF »
Heterochromatin Spreading at Yeast Telomeres Occurs in M Phase.
K. Martins-Taylor, M. L. Dula, and S. G. Holmes (2004)
Genetics 168, 65-75
   Abstract »    Full Text »    PDF »
The NAD+-dependent Sir2p histone deacetylase is a negative regulator of chromosomal DNA replication.
D. L. Pappas Jr., R. Frisch, and M. Weinreich (2004)
Genes & Dev. 18, 769-781
   Abstract »    Full Text »    PDF »
Genetic Interaction of an Origin Recognition Complex Subunit and the Polycomb Group Gene MEDEA during Seed Development.
M. A. Collinge, C. Spillane, C. Kohler, J. Gheyselinck, and U. Grossniklaus (2004)
PLANT CELL 16, 1035-1046
   Abstract »    Full Text »    PDF »
The Origin Recognition Complex and Sir4 Protein Recruit Sir1p to Yeast Silent Chromatin through Independent Interactions Requiring a Common Sir1p Domain.
M. E. Bose, K. H. McConnell, K. A. Gardner-Aukema, U. Muller, M. Weinreich, J. L. Keck, and C. A. Fox (2004)
Mol. Cell. Biol. 24, 774-786
   Abstract »    Full Text »    PDF »
SIR1 and the Origin of Epigenetic States in Saccharomyces cerevisiae.
L. PILLUS and J. RINE (2004)
Cold Spring Harb Symp Quant Biol 69, 259-266
   Abstract »    PDF »
Restructuring the Genome in Response to Adaptive Challenge: McClintock's Bold Conjecture Revisited.
R.A. JORGENSEN (2004)
Cold Spring Harb Symp Quant Biol 69, 349-354
   Abstract »    PDF »
The budding yeast silencing protein Sir1 is a functional component of centromeric chromatin.
J. A. Sharp, D. C. Krawitz, K. A. Gardner, C. A. Fox, and P. D. Kaufman (2003)
Genes & Dev. 17, 2356-2361
   Abstract »    Full Text »    PDF »
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 »
mRNAs Encoding Telomerase Components and Regulators Are Controlled by UPF Genes in Saccharomyces cerevisiae.
J. N. Dahlseid, J. Lew-Smith, M. J. Lelivelt, S. Enomoto, A. Ford, M. Desruisseaux, M. McClellan, N. Lue, M. R. Culbertson, and J. Berman (2003)
Eukaryot. Cell 2, 134-142
   Abstract »    Full Text »    PDF »
Cell-cycle control of the establishment of mating-type silencing in S. cerevisiae.
A. Lau, H. Blitzblau, and S. P. Bell (2002)
Genes & Dev. 16, 2935-2945
   Abstract »    Full Text »    PDF »
Inhibition of Polyomavirus ori-Dependent DNA Replication by mSin3B.
A.-Y. Xie and W. R. Folk (2002)
J. Virol. 76, 11809-11818
   Abstract »    Full Text »    PDF »
A Unique Class of Conditional sir2 Mutants Displays Distinct Silencing Defects in Saccharomyces cerevisiae.
S. N. Garcia and L. Pillus (2002)
Genetics 162, 721-736
   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 »
A Novel Yeast Silencer: The 2{micro} Origin of Saccharomyces cerevisiae Has HST3-, MIG1- and SIR-Dependent Silencing Activity.
A. Grunweller and A. E. Ehrenhofer-Murray (2002)
Genetics 162, 59-71
   Abstract »    Full Text »    PDF »
Functional Diversity of Silencers in Budding Yeasts.
J. O. O. Sjostrand, A. Kegel, and S. U. Astrom (2002)
Eukaryot. Cell 1, 548-557
   Abstract »    Full Text »    PDF »
A Role for the Saccharomyces cerevisiae RENT Complex Protein Net1 in HMR Silencing.
D. Kasulke, S. Seitz, and A. E. Ehrenhofer-Murray (2002)
Genetics 161, 1411-1423
   Abstract »    Full Text »    PDF »
Ordered Nucleation and Spreading of Silenced Chromatin in Saccharomyces cerevisiae.
L. N. Rusche, A. L. Kirchmaier, and J. Rine (2002)
Mol. Biol. Cell 13, 2207-2222
   Abstract »    Full Text »    PDF »
Steps in Assembly of Silent Chromatin in Yeast: Sir3-Independent Binding of a Sir2/Sir4 Complex to Silencers and Role for Sir2-Dependent Deacetylation.
G. J. Hoppe, J. C. Tanny, A. D. Rudner, S. A. Gerber, S. Danaie, S. P. Gygi, and D. Moazed (2002)
Mol. Cell. Biol. 22, 4167-4180
   Abstract »    Full Text »    PDF »
Transcriptional silencing in Saccharomyces cerevisiae and Schizosaccharomyces pombe.
Y. Huang (2002)
Nucleic Acids Res. 30, 1465-1482
   Abstract »    Full Text »    PDF »
The origin recognition complex: from simple origins to complex functions.
S. P. Bell (2002)
Genes & Dev. 16, 659-672
   Full Text »    PDF »
Conversion of a gene-specific repressor to a regional silencer.
L. N. R. a. J. Rine (2001)
Genes & Dev. 15, 955-967
   Abstract »    Full Text »
DNA Replication-Independent Silencing in S. cerevisiae.
A. L. Kirchmaier and J. Rine (2001)
Science 291, 646-650
   Abstract »    Full Text »
Establishment of Transcriptional Silencing in the Absence of DNA Replication.
Y.-C. Li, T.-H. Cheng, and M. R. Gartenberg (2001)
Science 291, 650-653
   Abstract »    Full Text »
The Sir1 protein's association with a silenced chromosome domain.
K. A. Gardner and C. A. Fox (2001)
Genes & Dev. 15, 147-157
   Abstract »    Full Text »
Acetylation of Histones and Transcription-Related Factors.
D. E. Sterner and S. L. Berger (2000)
Microbiol. Mol. Biol. Rev. 64, 435-459
   Abstract »    Full Text »    PDF »
Two Classes of sir3 Mutants Enhance the sir1 Mutant Mating Defect and Abolish Telomeric Silencing in Saccharomyces cerevisiae.
E. M. Stone, C. Reifsnyder, M. McVey, B. Gazo, and L. Pillus (2000)
Genetics 155, 509-522
   Abstract »    Full Text »
Identification of a Novel Allele of SIR3 Defective in the Maintenance, but Not the Establishment, of Silencing in Saccharomyces cerevisiae.
S. Enomoto, S. D. Johnston, and J. Berman (2000)
Genetics 155, 523-538
   Abstract »    Full Text »
Forkhead Genes in Transcriptional Silencing, Cell Morphology and the Cell Cycle: Overlapping and Distinct Functions for FKH1 and FKH2 in Saccharomyces cerevisiae.
P. C. Hollenhorst, M. E. Bose, M. R. Mielke, U. Müller, and C. A. Fox (2000)
Genetics 154, 1533-1548
   Abstract »    Full Text »
Yeast heterochromatin is a dynamic structure that requires silencers continuously.
T.-H. Cheng and M. R. Gartenberg (2000)
Genes & Dev. 14, 452-463
   Abstract »    Full Text »
Progression of meiotic DNA replication is modulated by interchromosomal interaction proteins, negatively by Spo11p and positively by Rec8p.
R. S. Cha, B. M. Weiner, S. Keeney, J. Dekker, and N. Kleckner (2000)
Genes & Dev. 14, 493-503
   Abstract »    Full Text »
A Role for the Replication Proteins PCNA, RF-C, Polymerase {epsilon} and Cdc45 in Transcriptional Silencing in Saccharomyces cerevisiae.
A. E. Ehrenhofer-Murray, R. T. Kamakaka, and J. Rine (1999)
Genetics 153, 1171-1182
   Abstract »    Full Text »
Identification of SAS4 and SAS5, Two Genes That Regulate Silencing in Saccharomyces cerevisiae.
E. Y. Xu, S. Kim, K. Replogle, J. Rine, and D. H. Rivier (1999)
Genetics 153, 13-23
   Abstract »    Full Text »
Histone Acetyltransferase HBO1 Interacts with the ORC1 Subunit of the Human Initiator Protein.
M. Iizuka and B. Stillman (1999)
J. Biol. Chem. 274, 23027-23034
   Abstract »    Full Text »    PDF »
Conservation of ARS Elements and Chromosomal DNA Replication Origins on Chromosomes III of Saccharomyces cerevisiae and S. carlsbergensis.
C. Yang, J. F. Theis, and C. S. Newlon (1999)
Genetics 152, 933-941
   Abstract »    Full Text »
A Genetic Screen for Ribosomal DNA Silencing Defects Identifies Multiple DNA Replication and Chromatin-Modulating Factors.
J. S. Smith, E. Caputo, and J. D. Boeke (1999)
Mol. Cell. Biol. 19, 3184-3197
   Abstract »    Full Text »    PDF »
Localization and Properties of a Silencing Element Near the mat3-M Mating-Type Cassette of Schizosaccharomyces pombe.
G. Thon, K. P. Bjerling, and I. S. Nielsen (1999)
Genetics 151, 945-963
   Abstract »    Full Text »
A Region of the Sir1 Protein Dedicated to Recognition of a Silencer and Required for Interaction with the Orc1 Protein in Saccharomyces cerevisiae.
K. A. Gardner, J. Rine, and C. A. Fox (1999)
Genetics 151, 31-44
   Abstract »    Full Text »
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
   Abstract »    Full Text »    PDF »
Homologs of the Yeast Longevity Gene LAG1 in Caenorhabditis elegans and Human.
J. C. Jiang, P. A. Kirchman, M. Zagulski, J. Hunt, and S. M. Jazwinski (1998)
Genome Res. 8, 1259-1272
   Abstract »    Full Text »
Identification of High-Copy Disruptors of Telomeric Silencing in Saccharomyces cerevisiae.
M. S. Singer, A. Kahana, A. J. Wolf, L. L. Meisinger, S. E. Peterson, C. Goggin, M. Mahowald, and D. E. Gottschling (1998)
Genetics 150, 613-632
   Abstract »    Full Text »
High-Resolution Structural Analysis of Chromatin at Specific Loci: Saccharomyces cerevisiae Silent Mating Type Locus HMLalpha.
K. Weiss and R. T. Simpson (1998)
Mol. Cell. Biol. 18, 5392-5403
   Abstract »    Full Text »
Distinct Cytoplasmic and Nuclear Fractions of Drosophila Heterochromatin Protein 1: Their Phosphorylation Levels and Associations with Origin Recognition Complex Proteins.
D. W. Huang, L. Fanti, D. T.S. Pak, M. R. Botchan, S. Pimpinelli, and R. Kellum (1998)
J. Cell Biol. 142, 307-318
   Abstract »    Full Text »    PDF »
Sir- and Silencer-Independent Disruption of Silencing in Saccharomyces by Sas10p.
R. T. Kamakaka and J. Rine (1998)
Genetics 149, 903-914
   Abstract »    Full Text »    PDF »
Studying the recruitment of Sp1 to the beta -globin promoter with an in vivo method: Protein position identification with nuclease tail (PIN*POINT).
J.-S. Lee, C.-H. Lee, and J. H. Chung (1998)
PNAS 95, 969-974
   Abstract »    Full Text »    PDF »
Chromatin assembly factor I contributes to the maintenance, but not the re-establishment, of silencing at the yeast silent mating loci.
S. Enomoto and J. Berman (1998)
Genes & Dev. 12, 219-232
   Abstract »    Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)