Mechanism of DNA damage responses mediated by acetylation of non-histone proteins

非组蛋白乙酰化介导的 DNA 损伤反应机制

• 批准号: 23651050
• 负责人: YASUDA Takeshi
• 金额: $ 2.58万
• 依托单位: National Institute of Radiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23651050/
• 关键词: DNA損傷応答; アセチル化; DNA修復; 相同組換え; ヌクレオチド除去修復; アポトーシス; 放射線; 幹細胞; 紫外線

We have newly identified several non-histone target proteins involved in DNA damage response, which are acetylated by histone acetyltransferases such as CBP and p300 in vitro. Among the identified acetylated proteins, acetylation of human Rad52 protein was induced after DNA double-strand break (DSB). We identified the acetylation sites of Rad52 by mass spectrometry with the in vitro- acetylated purified Rad52 protein. Radiation-induced homologous recombination was inhibited by mutations at the acetylated sites. Our results indicates that acetylation of Rad52 is required for DSB repair by homologous recombination.

我们新鉴定了几种参与 DNA 损伤反应的非组蛋白靶蛋白，这些蛋白在体外被组蛋白乙酰转移酶（如 CBP 和 p300）乙酰化。在已鉴定的乙酰化蛋白中，人 Rad52 蛋白的乙酰化是在 DNA 双链断裂 (DSB) 后诱导的。我们用体外乙酰化纯化的 Rad52 蛋白通过质谱法鉴定了 Rad52 的乙酰化位点。辐射诱导的同源重组受到乙酰化位点突变的抑制。我们的结果表明 Rad52 的乙酰化是同源重组 DSB 修复所必需的。

项目成果

Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

• DOI: 10.1016/j.ijrobp.2012.04.042
• 发表时间: 2013-02-01
• 期刊: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
• 影响因子: 7
• 作者: Nakayama, Fumiaki;Umeda, Sachiko;Imai, Takashi
• 通讯作者: Imai, Takashi

Analysis of molecular mechanisms underlying regulation of Rad52 function by acetylation

乙酰化调节Rad52功能的分子机制分析

• 发表时间: 2011
• 作者: Takuya Hino;Kengo Saito;Takeshi Yasuda;Takehiro Suzuki;Naoshi Dohmae;Wataru Kagawa;Hitoshi Kurumizaka
• 通讯作者: Hitoshi Kurumizaka

私の選択：研究者キャリアパスにおける岐路に立って

我的选择：处于研究职业道路的十字路口

• 发表时间: 2011
• 作者: 長倉千尋;月本光俊;小島周二;安田 武嗣
• 通讯作者: 安田 武嗣

The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation

• DOI: 10.1016/j.cell.2011.10.035
• 发表时间: 2011-11-23
• 期刊: CELL
• 影响因子: 64.5
• 作者: Fischer, Eric S.;Scrima, Andrea;Thomae, Nicolas H.
• 通讯作者: Thomae, Nicolas H.

Acetylation of human Rad52 protein by CBP/p300

CBP/p300 对人 Rad52 蛋白的乙酰化

• 发表时间: 2012
• 作者: Takeshi Yasuda;Kengo Saito;Wataru Kagawa;Tomoo Ogi;Takehiro Suzuki;Naoshi Dohmae;Takuya Hino;Yuka Nakazawa;Ai Saotome-Nakamura;Takamitsu Kato;Matthew Genet;Masaharu Hazawa;Masanori Tomita;Fumio Hanaoka;Kaoru Sugasawa;Penny Jeggo;Ryuichi Ok
• 通讯作者: Ryuichi Ok