title: Regulation of septin dynamics by the Saccharomyces cerevisiae lysine acetyltransferase NuA4.
abstract: In the budding yeast Saccharomyces cerevisiae, the lysine acetyltransferase NuA4 has been linked to a host of cellular processes through the acetylation of histone and non-histone targets. To discover proteins regulated by NuA4-dependent acetylation, we performed genome-wide synthetic dosage lethal screens to identify genes whose overexpression is toxic to non-essential NuA4 deletion mutants. The resulting genetic network identified a novel link between NuA4 and septin proteins, a group of highly conserved GTP-binding proteins that function in cytokinesis. We show that acetyltransferase-deficient NuA4 mutants have defects in septin collar formation resulting in the development of elongated buds through the Swe1-dependent morphogenesis checkpoint. We have discovered multiple sites of acetylation on four of the five yeast mitotic septins, Cdc3, Cdc10, Cdc12 and Shs1, and determined that NuA4 can acetylate three of the four in vitro. In vivo we find that acetylation levels of both Shs1 and Cdc10 are reduced in a catalytically inactive esa1 mutant. Finally, we determine that cells expressing a Shs1 protein with decreased acetylation in vivo have defects in septin localization that are similar to those observed in NuA4 mutants. These findings provide the first evidence that yeast septin proteins are acetylated and that NuA4 impacts septin dynamics.
authors: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors: Leslie
authors: L
authors: Mitchell
authors: Andrea
authors: A
authors: Lau
authors: Jean-Philippe
authors: JP
authors: Lambert
authors: Hu
authors: H
authors: Zhou
authors: Ying
authors: Y
authors: Fong
authors: Jean-François
authors: JF
authors: Couture
authors: Daniel
authors: D
authors: Figeys
authors: Kristin
authors: K
authors: Baetz
mesh_terms: D000107:Acetylation; D053263:Gene Regulatory Networks / Q000235:genetics; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D058112:Septins / Q000378:metabolism*; D013696:Temperature
chemical_list: D006657:Histones; D050505:Mutant Proteins; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; D058112:Septins; D008239:Lysine