Essential Functional Interactions of Saga, a Saccharomyces Cerevisiae Complex of Spt, Ada, and Gcn5 Proteins, with the Snf/Swi and Srb/Mediator Complexes

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The Saccharomyces cerevisiae transcription factor Spt20/Ada5 was originally identified by mutations that suppress Ty insertion alleles and by mutations that suppress the toxicity caused by Gal4-VP16 overexpression. Here we present evidence for physical associations between Spt20/Ada5 and three other Spt proteins, suggesting that they exist in a complex. A related study demonstrates that this complex also contains the histone acetyltransferase, Gcn5, and Ada2. This complex has been named SAGA (Spt/Ada/Gcn5 acetyltransferase). To identify functions that genetically interact with SAGA, we have screened for mutations that cause lethality in an spt20Δ/ada5Δ mutant. Our screen identified mutations in SNF2, SIN4, and GAL11. These mutations affect two known transcription complexes: Snf/Swi, which functions in nucleosome remodeling, and Srb/mediator, which is required for regulated transcription by RNA polymerase II. Systematic analysis has demonstrated that spt20Δ/ada5Δand spt7Δ mutations cause lethality with every snf/swi and srb/mediator mutation tested. Furthermore, a gcn5Δ mutation causes severe sickness with snf/swi mutations, but not with srb/mediator mutations. These findings suggest that SAGA has multiple activities and plays critical roles in transcription by RNA polymerase II.

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