Reference: McMahon SJ, et al. (2005) Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity. Proc Natl Acad Sci U S A 102(24):8478-82

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Abstract


Histone acetyltransferases have been shown to participate in many essential cellular processes, particularly those associated with activation of transcription. SAGA (Spt-Ada-Gcn5 acetyltransferase) and SLIK (SAGA-like) are two highly homologous multisubunit histone acetyltransferase complexes that were originally identified in the yeast Saccharomyces cerevisiae. Here, we identify the protein Sgf73/Sca7 as a component of SAGA and SLIK, and a homologue of the human SCA7-encoded protein ataxin-7, which, in its polyglutamine expanded pathological form, is responsible for the neurodegenerative disease spinocerebellar ataxia 7 (SCA7). Our findings indicate that yeast Sca7 is necessary for the integrity and function of both SAGA and SLIK, and that the human ataxin-7 is able to compliment the loss of Sca7 in yeast. A polyglutamine-expanded version of ataxin-7 assembles a SAGA complex that is depleted of critical proteins that regulate the ability of SAGA to acetylate nucleosomes. These observations have significant implications for the function of the human Sca7 protein in disease pathogenesis.

Reference Type
Comparative Study | Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
McMahon SJ, Pray-Grant MG, Schieltz D, Yates JR, Grant PA
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Gene Ontology Annotations


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Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

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GenePhenotypeExperiment TypeMutant InformationStrain BackgroundChemicalDetails
SGF73vegetative growth: decreased
classical geneticsnull
Allele: sca7Δ
S288CMedia: media containing acetate or glycerol and ethanol as the carbon source or sc media lacking inositol
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Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

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Gene Species Gene ID Strain background Direction Details Source Reference