ATMに依存するクロマチンの変化は,シスからDNAへの転写を沈黙させ,二重鎖の断裂を引き起こします

Niraj M Shanbhag¹, Ilona U Rafalska-Metcalf, Carlo Balane-Bolivar

¹Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.

Cell

|June 17, 2010

まとめ

DNAの二重鎖の断裂はATMキナーゼに依存した転写サイレンスプログラムを誘発する. このプロセスはヒストンの汎用化を含み,DNAの断裂の近くのクロマチンの構造に影響します.

科学分野:

分子生物学は分子生物学である.
遺伝学遺伝学とは
細胞生物学細胞生物学

背景:

DNAの二重鎖断裂 (DSB) は,クロマチンの重要な変化を誘発する.
ATMキナーゼは,DSBに対する細胞応答において重要な役割を果たします.
ヒストンH2Aの普遍化 (uH2A) は,DSB修復と転写抑制と関連しています.

研究の目的:

uH2A媒介の転写抑制がDSBsの文脈で保存されているという仮説を検証する.
DSBのATMに依存したトランスクリプションサイレンスプログラムを特徴づける.
DSB誘発の静音化およびその逆転に関与する分子プレーヤーを特定する.

主な方法:

修復タンパク質の募集と局所転写の単細胞可視化のための新しいレポーターシステムを利用しました.
ATM,RNF8,RNF168,USP16がDSB付近の転写調節における役割を評価するために遺伝的アプローチを用いた.

主要な成果:

cisからDSBで発生するATM依存の転写静音化プログラムについて説明しました.
ATMがRNAポリメラーゼIIの延伸依存クロマチンの脱凝縮をDSBから遠隔に防ぐことが実証されました.
RNF8とRNF168に対する静音化の部分的依存と,静音化の逆転のUSP16への依存を示した.

結論:

ATMキナーゼは,DNAの二重鎖の断裂に反応して,トランスクリプションサイレンスプログラムをオーケストラ化します.
uH2Aを含む翻訳後の改変は,DNA修復と転写調節の間の交響を媒介する.
この発見は,DNA損傷反応中のクロマチンの改変の複雑な相互作用についての洞察を提供します.

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