title: Two Drosophila Ada2 homologues function in different multiprotein complexes.
abstract: The reversible acetylation of the N-terminal tails of histones is crucial for transcription, DNA repair, and replication. The enzymatic reaction is catalyzed by large multiprotein complexes, of which the best characterized are the Gcn5-containing N-acetyltransferase (GNAT) complexes. GNAT complexes from yeast to humans share several conserved subunits, such as Ada2, Ada3, Spt3, and Tra1/TRRAP. We have characterized these factors in Drosophila and found that the flies have two distinct Ada2 variants (dAda2a and dAda2b). Using a combination of biochemical and cell biological approaches we demonstrate that only one of the two Drosophila Ada2 homologues, dAda2b, is a component of Spt-Ada-Gcn5-acetyltransferase (SAGA) complexes. The other Ada2 variant, dAda2a, can associate with dGcn5 but is not incorporated into dSAGA-type complexes. This is the first example of a complex-specific association of the Ada-type transcriptional adapter proteins with GNATs. In addition, dAda2a is part of Gcn5-independent complexes, which are concentrated at transcriptionally active regions on polytene chromosomes. This implicates novel functions for dAda2a in transcription. Humans and mice also possess two Ada2 variants with high homology to dAda2a and dAda2b, respectively. This suggests that the mammalian and fly homologues of the transcriptional adapter Ada2 form two functionally distinct subgroups with unique characteristics.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kusch
authors.forename: Sebastián
authors.initials: S
authors.lastname: Guelman
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D010802:Phylogeny; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D029721:Drosophila Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D051548:Histone Acetyltransferases; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011506:Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C470558:Ada2a protein, Drosophila; C474203:p53 protein, Drosophila; C470559:ADA3 protein, Drosophila; C470557:GCN5 protein, Drosophila; D000099224:p300-CBP-Associated Factor