Restoration of Silencing in Saccharomyces cerevisiae by Tethering of a Novel Sir2-Interacting Protein, Esc8

Corresponding author: David Shore, University of Geneva, 30, Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland., david.shore{at}molbio.unige.ch (E-mail)

Communicating editor: M. JOHNSTON

We previously described two classes of SIR2 mutations specifically defective in either telomeric/HM silencing (class I) or rDNA silencing (class II) in S. cerevisiae. Here we report the identification of genes whose protein products, when either overexpressed or directly tethered to the locus in question, can establish silencing in SIR2 class I mutants. Elevated dosage of SCS2, previously implicated as a regulator of both inositol biosynthesis and telomeric silencing, suppressed the dominant-negative effect of a SIR2-143 mutation. In a genetic screen for proteins that restore silencing when tethered to a telomere, we isolated ESC2 and an uncharacterized gene, (YOL017w), which we call ESC8. Both Esc2p and Esc8p interact with Sir2p in two-hybrid assays, and the Esc8p-Sir2 interaction is detected in vitro. Interestingly, Esc8p has a single close homolog in yeast, the ISW1-complex factor Ioc3p, and has also been copurified with Isw1p, raising the possibility that Esc8p is a component of an Isw1p-containing nucleosome remodeling complex. Whereas esc2 and esc8 deletion mutants alone have only marginal silencing defects, cells lacking Isw1p show a strong silencing defect at HMR but not at telomeres. Finally, we show that Esc8p interacts with the Gal11 protein, a component of the RNA pol II mediator complex.

This article has been cited by other articles:

				M. Pinskaya, A. Nair, D. Clynes, A. Morillon, and J. Mellor Nucleosome Remodeling and Transcriptional Repression Are Distinct Functions of Isw1 in Saccharomyces cerevisiae Mol. Cell. Biol., May 1, 2009; 29(9): 2419 - 2430. [Abstract] [Full Text] [PDF]

				J. Sollier, R. Driscoll, F. Castellucci, M. Foiani, S. P. Jackson, and D. Branzei The Saccharomyces cerevisiae Esc2 and Smc5-6 Proteins Promote Sister Chromatid Junction-mediated Intra-S Repair Mol. Biol. Cell, March 15, 2009; 20(6): 1671 - 1682. [Abstract] [Full Text] [PDF]

				H. W. Mankouri, H.-P. Ngo, and I. D. Hickson Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway in Saccharomyces cerevisiae Mol. Biol. Cell, March 15, 2009; 20(6): 1683 - 1694. [Abstract] [Full Text] [PDF]

				T. Ohya, H. Arai, Y. Kubota, H. Shinagawa, and T. Hishida A SUMO-Like Domain Protein, Esc2, Is Required for Genome Integrity and Sister Chromatid Cohesion in Saccharomyces cerevisiae Genetics, September 1, 2008; 180(1): 41 - 50. [Abstract] [Full Text] [PDF]

				C. J.R. Loewen, B. P. Young, S. Tavassoli, and T. P. Levine Inheritance of cortical ER in yeast is required for normal septin organization J. Cell Biol., November 5, 2007; 179(3): 467 - 483. [Abstract] [Full Text] [PDF]

				J. Mead, R. McCord, L. Youngster, M. Sharma, M. R. Gartenberg, and A. K. Vershon Swapping the Gene-Specific and Regional Silencing Specificities of the Hst1 and Sir2 Histone Deacetylases Mol. Cell. Biol., April 1, 2007; 27(7): 2466 - 2475. [Abstract] [Full Text] [PDF]

				M. Veron, Y. Zou, Q. Yu, X. Bi, A. Selmi, E. Gilson, and P.-A. Defossez Histone H1 of Saccharomyces cerevisiae Inhibits Transcriptional Silencing Genetics, June 1, 2006; 173(2): 579 - 587. [Abstract] [Full Text] [PDF]

				C. J. R. Loewen and T. P. Levine A Highly Conserved Binding Site in Vesicle-associated Membrane Protein-associated Protein (VAP) for the FFAT Motif of Lipid-binding Proteins J. Biol. Chem., April 8, 2005; 280(14): 14097 - 14104. [Abstract] [Full Text] [PDF]

				H. Morikawa, T. Morishita, S. Kawane, H. Iwasaki, A. M. Carr, and H. Shinagawa Rad62 Protein Functionally and Physically Associates with the Smc5/Smc6 Protein Complex and Is Required for Chromosome Integrity and Recombination Repair in Fission Yeast Mol. Cell. Biol., November 1, 2004; 24(21): 9401 - 9413. [Abstract] [Full Text] [PDF]

				M. Oki, L. Valenzuela, T. Chiba, T. Ito, and R. T. Kamakaka Barrier Proteins Remodel and Modify Chromatin To Restrict Silenced Domains Mol. Cell. Biol., March 1, 2004; 24(5): 1956 - 1967. [Abstract] [Full Text] [PDF]

				E. D. Andrulis, D. C. Zappulla, K. Alexieva-Botcheva, C. Evangelista, and R. Sternglanz One-Hybrid Screens at the Saccharomyces cerevisiae HMR Locus Identify Novel Transcriptional Silencing Factors Genetics, January 1, 2004; 166(1): 631 - 635. [Abstract] [Full Text] [PDF]

				S. Kagiwada and R. Zen Role of the Yeast VAP Homolog, Scs2p, in INO1 Expression and Phospholipid Metabolism J. Biochem., April 1, 2003; 133(4): 515 - 522. [Abstract] [Full Text] [PDF]