TY - JOUR
T1 - DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics
AU - Ikura, Tsuyoshi
AU - Tashiro, Satoshi
AU - Kakino, Akemi
AU - Shima, Hiroki
AU - Jacob, Naduparambil
AU - Amunugama, Ravindra
AU - Yoder, Kristine
AU - Izumi, Shunsuke
AU - Kuraoka, Isao
AU - Tanaka, Kiyoji
AU - Kimura, Hiroshi
AU - Ikura, Masae
AU - Nishikubo, Shuichi
AU - Ito, Takashi
AU - Muto, Akihiko
AU - Miyagawa, Kiyoshi
AU - Takeda, Shunichi
AU - Fishel, Richard
AU - Igarashi, Kazuhiko
AU - Kamiya, Kenji
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00579-07
DO - 10.1128/MCB.00579-07
M3 - Article
C2 - 17709392
AN - SCOPUS:35148894396
VL - 27
SP - 7028
EP - 7040
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 20
ER -