title: Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin.
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.
authors.affiliation: Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Ikura
authors.affiliation: Department of Radiation Systems, Radiation Biology Center, Kyoto University, Kyoto, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Laboratory of Environment Quality Management, Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsuda
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shima
authors.affiliation: National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Adachi
authors.affiliation: Laboratory of Environment Quality Management, Research Center for Environmental Quality Management, Kyoto University, Otsu, Shiga, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Shiraki
authors.affiliation: Laboratory of Chromatin Regulatory Network, Department of Mutagenesis, Radiation Biology Center, Kyoto University, Kyoto, Japan ikurat@house.rbc.kyoto-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
mesh_terms: D000107:Acetylation; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones; C112156:NBN protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D004247:DNA; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5