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Genetic evidence links the ASTRA protein chaperone component Tti2 to the SAGA transcription factor Tra1.

Tra1 is a 3744-residue component of the Saccharomyces cerevisiae SAGA, NuA4, and ASTRA complexes. Tra1 contains essential C-terminal PI3K and FATC domains, but unlike other PIKK (phosphoinositide three-kinase-related kinase) family members, lacks kinase activity. To analyze functions of the FATC domain, we selected for suppressors of tra1-F3744A, an allele that results in slow growth under numerous conditions of stress. Two alleles of TTI2, tti2-F328S and tti2-I336F, acted in a partially dominant fashion to suppress the growth-related phenotypes associated with tra1-F3744A as well as its resulting defects in transcription. tti2-F328S suppressed an additional FATC domain mutation (tra1-L3733A), but not a mutation in the PI3K domain or deletions of SAGA or NuA4 components. We find eGFP-tagged Tti2 distributed throughout the cell. Tti2 is a component of the ASTRA complex, and in mammalian cells associates with molecular chaperones in complex with Tti1 and Tel2. Consistent with this finding, Tra1 levels are reduced in a strain with a temperature-sensitive allele of tel2. Further agreeing with a possible role for Tti2 in the folding or stabilization of Tra1, tra1-F3744A was mislocalized to the cytoplasm, particularly under conditions of stress. Since an intragenic mutation of tra1-R3590I also suppressed F3744A, we propose that Tti2 is required for the folding/stability of the C-terminal FATC and PI3K domains of Tra1 into their functionally active form.

Pubmed ID: 22505622

Authors

  • Genereaux J
  • Kvas S
  • Dobransky D
  • Karagiannis J
  • Gloor GB
  • Brandl CJ

Journal

Genetics

Publication Data

July 12, 2012

Associated Grants

  • Agency: Canadian Institutes of Health Research, Id: MOP10845

Mesh Terms

  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Ethanol
  • Histone Acetyltransferases
  • Molecular Chaperones
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Protein Transport
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Temperature
  • Trans-Activators
  • Transcription, Genetic