title: DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics.
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.
authors: Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryoumachi 2-1, Aobaku Sendai 980-8575, Japan. ikurat@mail.tains.tohoku.ac.jp
authors: Tsuyoshi
authors: T
authors: Ikura
authors: Satoshi
authors: S
authors: Tashiro
authors: Akemi
authors: A
authors: Kakino
authors: Hiroki
authors: H
authors: Shima
authors: Naduparambil
authors: N
authors: Jacob
authors: Ravindra
authors: R
authors: Amunugama
authors: Kristine
authors: K
authors: Yoder
authors: Shunsuke
authors: S
authors: Izumi
authors: Isao
authors: I
authors: Kuraoka
authors: Kiyoji
authors: K
authors: Tanaka
authors: Hiroshi
authors: H
authors: Kimura
authors: Masae
authors: M
authors: Ikura
authors: Shuichi
authors: S
authors: Nishikubo
authors: Takashi
authors: T
authors: Ito
authors: Akihiko
authors: A
authors: Muto
authors: Kiyoshi
authors: K
authors: Miyagawa
authors: Shunichi
authors: S
authors: Takeda
authors: Richard
authors: R
authors: Fishel
authors: Kazuhiko
authors: K
authors: Igarashi
authors: Kenji
authors: K
authors: Kamiya
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D010766:Phosphorylation; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C471607:UBE2N protein, human; D044763:Ubiquitin-Conjugating Enzymes
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