ブロモドメインタンパク質 Brd4 は,DNA 損傷信号からクロマチンを隔離します
Scott R Floyd1, Michael E Pacold, Qiuying Huang
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|June 4, 2013
まとめ
Brd4タンパク質の特定の形態は,DNA損傷応答シグナリングのブレーキとして作用する. この発見は,Brd4を明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- DNAの損傷は複雑な信号ネットワークを誘発し,細胞サイクルを停止したり,DNAを修復したり,細胞死を誘発します.
- 染色体構造は,DNA損傷反応の開始と拡散において重要な役割を果たします.
- BET (ブロモドメインおよびエクストラターミナル) 家族のメンバーであるBrd4は,転写制御における役割で知られています.
研究 の 目的:
- DNA損傷反応におけるクロマチンの構造の役割を調査する.
- イオン化放射線誘発シグナル伝達に関与するクロマチンの改変および相互作用する遺伝子を特定する.
- DNA損傷反応経路における Brd4 アイソフォームの機能を明らかにする.
主な方法:
- クロマチンを改変し相互作用する遺伝子の高濃度複合RNA媒介干渉 (RNAi) スクリーン.
- イオン化する放射線によって誘発されたシグナル伝達および応答イベントの監視.
- Brd4がクロマチンとコンデンシンII複合体との相互作用を調査する.
主要な成果:
- Brd4のイソフォームは,DNA損傷応答シグナル伝達の内生性阻害剤として作用する.
- Brd4は,ブロモドメイン相互作用を通じてコンデンシンII複合体をアセチルヒストンに誘導する.
- この Brd4 アイソフォームの喪失は,クロマチンの緩和,細胞サイクル回復の加速,放射線照射後の生存率の増加につながる.
- この Brd4 アイソフォームの機能の獲得はクロマチンを圧縮し,DNA損傷応答シグナルを弱め,放射線誘発による致死性を高めます.
結論:
- Brd4は,DNA損傷に対するシグナル応答を調節するクロマチンの絶縁剤として機能します.
- 特定の Brd4 アイソフォームは,DNA 損傷に対する細胞の反応を微調整し,細胞の運命に影響を与えます.
- Brd4をターゲットにすることは,さまざまな文脈でDNA損傷反応を管理するための治療戦略を提供することができます.
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