Genetics, Vol 147, 451-465, Copyright © 1997

INVESTIGATIONS

Essential Functional Interactions of SAGA, a Saccharomyces cerevisiae Complex of Spt, Ada, and Gcn5 Proteins, With the Snf/Swi and Srb/Mediator Complexes

S. M. Roberts and F. Winston
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115

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 spt20{Delta}/ada5{Delta} 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 spt20{Delta}/ada5{Delta}and spt7{Delta} mutations cause lethality with every snf/swi and srb/mediator mutation tested. Furthermore, a gcn5{Delta} 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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