Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75

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

Research output: Contribution to journalArticle

86 Scopus citations

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 2008

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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