A role for Sds3p, a component of the Rpd3p/Sin3p deacetylase complex, in maintaining cellular integrity in Saccharomyces cerevisiae

The SDS3 gene was identified in a suppressor screen for mutations that enha nce position-effect silencing in yeast. Cells that are defective in SDS3 ha ve pleiotropic phenotypes, similar to those seen in the absence of the hist one deacetylase components Rpd3p and Sin3p, including meiotic defects and i mproper regulation of the HO gene. To gain further insight into SDS3 functi on we undertook an epistasis analysis with other SDS genes. We found that s ds3 is synthetically lethal in combination with a deletion of the SWI6 (SDS 11) gene, which encodes a cell-cycle regulator. sds3 swi6 double mutants do not display a specific cell-cycle arrest phenotype, but instead die due to cell lysis. Constitutive expression of the Gt cyclin gene CLN2 restores vi ability to an sds3 swi6 strain, as does overexpression of SKT5/CHS4, which encodes a regulatory subunit of chitin synthase III, and SSD1, a gene previ ously implicated in ensuring cell-cycle progression and cellular integrity. Significantly, growth in the presence of 1 M sorbitol or overexpression of PKC1 also partially suppresses the lethal phenotype of the sds3 swi6 strai n. This lethality in the absence of SWI6 function most probably reflects an important or essential role for Sds3p in the Rpd3p/Sin3p historic deacetyl ase complex, since RPD3 and SINS mutations are also synthetically lethal in combination with swi6 and these phenotypes are also rescued by elevated do sage 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 pathways to activate genes required for cell wall biosynthesis.