title: Yaf9, a novel NuA4 histone acetyltransferase subunit, is required for the cellular response to spindle stress in yeast.
abstract: Yaf9 is one of three proteins in budding yeast containing a YEATS domain. We show that Yaf9 is part of a large complex and that it coprecipitates with three known subunits of the NuA4 histone acetyltransferase. Although Esa1, the catalytic subunit of NuA4, is essential for viability, we found that yaf9 Delta mutants are viable but hypersensitive to microtubule depolymerizing agents and synthetically lethal with two different mutants of the mitotic apparatus. Microtubules depolymerized more readily in the yaf9Delta mutant compared to the wild type in the presence of nocodazole, and recovery of microtubule polymerization and cell division from limiting concentrations of nocodazole was inhibited. Two other NuA4 mutants (esa1-1851 and yng2 Delta) and nonacetylatable histone H4 mutants were also sensitive to benomyl. Furthermore, wild-type budding yeast were more resistant to benomyl when grown in the presence of trichostatin A, a histone deacetylase inhibitor. These results strongly suggest that acetylation of histone H4 by NuA4 is required for the cellular resistance to spindle stress.
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, 91191 Gif-sur-Yvette, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Le Masson
authors.forename: David Y
authors.initials: DY
authors.lastname: Yu
authors.forename: Kurt
authors.initials: K
authors.lastname: Jensen
authors.forename: Anne
authors.initials: A
authors.lastname: Chevalier
authors.forename: Régis
authors.initials: R
authors.lastname: Courbeyrette
authors.forename: Yves
authors.initials: Y
authors.lastname: Boulard
authors.forename: M Mitchell
authors.initials: MM
authors.lastname: Smith
authors.forename: Carl
authors.initials: C
authors.lastname: Mann
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D001542:Benomyl / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases; D006877:Hydroxamic Acids / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C465210:Act1 protein, S cerevisiae; D000199:Actins; C088827:Arp4 protein, S cerevisiae; D002843:Chromatin; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D006877:Hydroxamic Acids; C120755:MPS2 protein, S cerevisiae; D008565:Membrane Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C477280:YAF9 protein, S cerevisiae; C012589:trichostatin A; D000123:Acetyltransferases; C428131:Eaf3 protein, S cerevisiae; C469780:Yng2 protein, S cerevisiae; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases; D015739:Nocodazole; D001542:Benomyl