title: Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes.
abstract: Acetylation of histone H3 on lysine 56 occurs during mitotic and meiotic S phase in fungal species. This acetylation blocks a direct electrostatic interaction between histone H3 and nucleosomal DNA, and the absence of this modification is associated with extreme sensitivity to genotoxic agents. We show here that H3-K56 acetylation is catalyzed when Rtt109, a protein that lacks significant homology to known acetyltransferases, forms an active complex with either of two histone binding proteins, Asf1 or Vps75. Rtt109 binds to both these cofactors, but not to histones alone, forming enzyme complexes with kinetic parameters similar to those of known histone acetyltransferase (HAT) enzymes. Therefore, H3-K56 acetylation is catalyzed by a previously unknown mechanism that requires a complex of two proteins: Rtt109 and a histone chaperone. Additionally, these complexes are functionally distinct, with the Rtt109/Asf1 complex, but not the Rtt109/Vps75 complex, being critical for resistance to genotoxic agents.
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street #506, Worcester, MA 01605, USA.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tsubota
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Berndsen
authors.forename: Judith A
authors.initials: JA
authors.lastname: Erkmann
authors.forename: Corey L
authors.initials: CL
authors.lastname: Smith
authors.forename: Lanhao
authors.initials: L
authors.lastname: Yang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
authors.forename: John M
authors.initials: JM
authors.lastname: Denu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kaufman
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002645:Chickens; D003067:Coenzymes / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: C109731:ASF1 protein, S cerevisiae; D000596:Amino Acids; D018797:Cell Cycle Proteins; D003067:Coenzymes; D004271:DNA, Fungal; D006657:Histones; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D021122:Protein Subunits; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D008239:Lysine