Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75

Christopher E. Berndsen, Toshiaki Tsubota, Scott Eugene Lindner, Susan Lee, James M. Holton, Paul D. Kaufman, James L. Keck, John M. Denu

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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 ∼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 Rtt109. 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.

Original languageEnglish (US)
Pages (from-to)948-956
Number of pages9
JournalNature Structural and Molecular Biology
Volume15
Issue number9
DOIs
StatePublished - Sep 1 2008

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Histone Chaperones
Histone Acetyltransferases
Histones
Acetylation
Nucleosomes
Molecular Biology
Histone Code
S Phase
DNA Repair
Lysine
DNA Damage
Saccharomyces cerevisiae
X-Rays
DNA

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Berndsen, C. E., Tsubota, T., Lindner, S. E., Lee, S., Holton, J. M., Kaufman, P. D., ... Denu, J. M. (2008). Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75. Nature Structural and Molecular Biology, 15(9), 948-956. https://doi.org/10.1038/nsmb.1459
Berndsen, Christopher E. ; Tsubota, Toshiaki ; Lindner, Scott Eugene ; Lee, Susan ; Holton, James M. ; Kaufman, Paul D. ; Keck, James L. ; Denu, John M. / Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75. In: Nature Structural and Molecular Biology. 2008 ; Vol. 15, No. 9. pp. 948-956.
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Berndsen, CE, Tsubota, T, Lindner, SE, Lee, S, Holton, JM, Kaufman, PD, Keck, JL & Denu, JM 2008, 'Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75', Nature Structural and Molecular Biology, vol. 15, no. 9, pp. 948-956. https://doi.org/10.1038/nsmb.1459

Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75. / Berndsen, Christopher E.; Tsubota, Toshiaki; Lindner, Scott Eugene; Lee, Susan; Holton, James M.; Kaufman, Paul D.; Keck, James L.; Denu, John M.

In: Nature Structural and Molecular Biology, Vol. 15, No. 9, 01.09.2008, p. 948-956.

Research output: Contribution to journalArticle

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