DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics

Tsuyoshi Ikura, Satoshi Tashiro, Akemi Kakino, Hiroki Shima, Naduparambil Jacob, Ravindra Amunugama, Kristine Yoder, Shunsuke Izumi, Isao Kuraoka, Kiyoji Tanaka, Hiroshi Kimura, Masae Ikura, Shuichi Nishikubo, Takashi Ito, Akihiko Muto, Kiyoshi Miyagawa, Shunichi Takeda, Richard Fishel, Kazuhiko Igarashi, Kenji Kamiya

Research output: Contribution to journalArticlepeer-review

273 Citations (Scopus)

Abstract

Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.

Original languageEnglish
Pages (from-to)7028-7040
Number of pages13
JournalMolecular and cellular biology
Volume27
Issue number20
DOIs
Publication statusPublished - 2007 Oct

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics'. Together they form a unique fingerprint.

Cite this