Tip60によるアセチル化は,DNA病変における選択的なヒストン変異体交換のために必要である

Thomas Kusch¹, Laurence Florens, W Hayes Macdonald

¹Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. tnk@stowers-institute.org

Science (New York, N.Y.)

|November 6, 2004

まとめ

ドロソフィラTip60複合体は,酸化H2Av.をアセチル化および交換することによってDNA損傷の痕跡を除去します. これは,選択的なヒストンの改変と修復のための新しいメカニズムを明らかにします.

科学分野:

分子生物学は分子生物学である.
エピジェネティクスエピジェネティクス
DNA修復 DNA修復する

背景:

ヒストン変異体H2A.Xのリン酸化は,DNAの二重鎖の断裂に対する急速な反応である.
DNA修復過程における,リン酸化H2A.X (フォスフォ-H2Av) の正確な機能と除去は,ほとんど特徴づけられていない.

研究の目的:

ドロソフィラ・メラノガスターのDNA修復中のフォスフォ-H2Av除去のメカニズムを調査する.
H2Avのリン酸化を逆転させるタンパク質複合体を特定する.

主な方法:

Drosophila melanogasterをモデル生物として利用しました.
ドロソフィラTip60染色体改造複合体の役割を調査した.
複合体内のヒストンアセチルトランスファーゼ (HAT) とATPアゼの酵素活性を調べました.

主要な成果:

ドロソフィラTip60複合体は,核体ホルモン-H2Av.をアセチル化する.
dTip60複合体は,改変されていないH2Av.とフォスフォ-H2Avの交換を容易にする.
dTip60 HATとDomino/p400 ATPaseのコンポーネントは,両方とも,フォスフォ-H2Av交換に不可欠である.

結論:

fosfo-H2Avのアセチル化と除去を含む選択的なヒストン交換のための新しいメカニズムが特定されました.
dTip60複合体内の異なる染色体再構成酵素の協調した作用が,このプロセスを指揮する.
この発見は,DNA修復中のクロマチンの変化の動的調節に光を当てています.

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