A role for Sds3p, a component of the Rpd3p/Sin3p deacetylase complex, in maintaining cellular integrity in Saccharomyces
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O R I GI N A L P A P E R
D. Vannier á P. Damay á D. Shore
A role for Sds3p, a component of the Rpd3p/Sin3p deacetylase complex, in maintaining cellular integrity in Saccharomyces cerevisiae
Received: 3 July 2000 / Accepted: 15 December 2000 / Published online: 14 March 2001 Ó Springer-Verlag 2001
Abstract The SDS3 gene was identi®ed in a suppressor screen for mutations that enhance position-eect silencing in yeast. Cells that are defective in SDS3 have pleiotropic phenotypes, similar to those seen in the absence of the histone deacetylase components Rpd3p and Sin3p, including meiotic defects and improper regulation of the HO gene. To gain further insight into SDS3 function we undertook an epistasis analysis with other SDS genes. We found that sds3 is synthetically lethal in combination with a deletion of the SWI6 (SDS11) gene, which encodes a cell-cycle regulator. sds3 swi6 double mutants do not display a speci®c cell-cycle arrest phenotype, but instead die due to cell lysis. Constitutive expression of the G1 cyclin gene CLN2 restores viability to an sds3 swi6 strain, as does overexpression of SKT5/ CHS4, which encodes a regulatory subunit of chitin synthase III, and SSD1, a gene previously implicated in ensuring cell-cycle progression and cellular integrity. Signi®cantly, growth in the presence of 1 M sorbitol or overexpression of PKC1 also partially suppresses the lethal phenotype of the sds3 swi6 strain. This lethality in the absence of SWI6 function most probably re¯ects an important or essential role for Sds3p in the Rpd3p/Sin3p histone deacetylase complex, since RPD3 and SIN3 mutations are also synthetically lethal in combination with swi6 and these phenotypes are also rescued by elevated dosage of SKT5/CHS4, SSD1, or PCK1. Taken together, these data indicate that the transcription factor Swi6p and the Rpd3p-based deacetylase complex act in parallel Communicated by C. P. Hollenberg D. Vannier Department of Microbiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA P. Damay á D. Shore (&) Department of Molecular Biology, University of Geneva, 30, quai Ernest-Ansermet, 1211 Geneva 4, Switzerland E-mail: [email protected] Tel.: +41-22-7026183 Fax: +41-22-7026868
pathways to activate genes required for cell wall biosynthesis. Key words Yeast á Transcriptional silencing á Cell wall biosynthesis á Swi6p á PKC
Introduction Transcriptional silencing at the HM mating-type loci and telomeres in yeast is due to a SIR protein-mediated alteration in chromatin that aects transcription, replication, and DNA repair (Hecht et al. 1995, 1996; reviewed by Gartenberg 2000). One of the proteins that binds to these loci and initiates this change in chromatin structure is the multifunctional and essential transcriptional regulator Rap1p (reviewed in Shore 1994). Mutations in RAP1 have been identi®ed that genetically separate the silencing function of the protein from its (presumably) essential activation function (Sussel and Shore 1991; Kyrion et al. 1993; Liu et al. 1994). One
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