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Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75.

Histone acetylation and nucleosome remodeling regulate DNA damage repair, replication and transcription. Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones. In vitro analysis of Rtt109 revealed that Vps75, a Nap1 family histone chaperone, could also stimulate Rtt109-dependent acetylation of H3K56. However, the molecular function of the Rtt109-Vps75 complex remains elusive. Here we have probed the molecular functions of Vps75 and the Rtt109-Vps75 complex through biochemical, structural and genetic means. We find that Vps75 stimulates the kcat of histone acetylation by approximately 100-fold relative to Rtt109 alone and enhances acetylation of K9 in the H3 histone tail. Consistent with the in vitro evidence, cells lacking Vps75 showed a substantial reduction (60%) in H3K9 acetylation during S phase. X-ray structural, biochemical and genetic analyses of Vps75 indicate a unique, structurally dynamic Nap1-like fold that suggests a potential mechanism of Vps75-dependent activation of Rttl09. Together, these data provide evidence for a multifunctional HAT-chaperone complex that acetylates histone H3 and deposits H3-H4 onto DNA, linking histone modification and nucleosome assembly.

Pubmed ID: 19172748


  • Berndsen CE
  • Tsubota T
  • Lindner SE
  • Lee S
  • Holton JM
  • Kaufman PD
  • Keck JL
  • Denu JM


Nature structural & molecular biology

Publication Data

September 27, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM055712
  • Agency: NIGMS NIH HHS, Id: GM059785
  • Agency: NIGMS NIH HHS, Id: R01 GM055712
  • Agency: NIGMS NIH HHS, Id: R01 GM055712-08
  • Agency: NIGMS NIH HHS, Id: R01 GM059785
  • Agency: NIGMS NIH HHS, Id: R01 GM059785-08

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • Enzyme Activation
  • Histone Acetyltransferases
  • Histones
  • In Vitro Techniques
  • Kinetics
  • Models, Molecular
  • Molecular Chaperones
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Static Electricity
  • Substrate Specificity
  • Xenopus Proteins
  • Xenopus laevis