2. Academic Validation
  3. Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin

Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin

  • Mol Cell Biol. 2015 Dec;35(24):4147-57. doi: 10.1128/MCB.00757-15.
Masae Ikura 1,  Kanji Furuya 2,  Shun Matsuda 3,  Ryo Matsuda 1,  Hiroki Shima 4,  Jun Adachi 5,  Tomonari Matsuda 3,  Takuma Shiraki 6,  Tsuyoshi Ikura 7
Affiliations

Affiliations

  • 1 Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto, Japan.
  • 2 Department of Radiation Systems, Radiation Biology Center, Kyoto University, Kyoto, Japan.
  • 3 Laboratory of Environment Quality Management, Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, Japan.
  • 4 Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 5 National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
  • 6 Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan.
  • 7 Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto, Japan ikurat@house.rbc.kyoto-u.ac.jp.
PMID: 26438602 DOI: 10.1128/MCB.00757-15
Abstract

The association and dissociation of DNA damage response (DDR) factors with damaged chromatin occurs dynamically, which is crucial for the activation of DDR signaling in a spatiotemporal manner. We previously showed that the TIP60 Histone Acetyltransferase complex acetylates histone H2AX, to facilitate H2AX exchange at sites of DNA damage. However, it remained unclear how the acetylation of histone H2AX by TIP60 is related to the DDR signaling. We found that the acetylation but not the phosphorylation of H2AX is essential for the turnover of NBS1 on damaged chromatin. The loss of H2AX acetylation at Lys 5 by TIP60 in cells disturbed the accumulation of NBS1 at sites of DNA damage. Although the phosphorylation of H2AX is also reportedly required for the retention of NBS1 at damage sites, our data indicated that the acetylation-dependent NBS1 turnover by TIP60 on damaged chromatin restricts the dispersal of NBS1 foci from the sites of DNA damage. These findings indicate the importance of the acetylation-dependent dynamic binding of NBS1 to damaged chromatin, created by histone H2AX exchange, for the proper accumulation of NBS1 at DNA damage sites.

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