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Chk1はヒストンH3スレオニン11キナーゼで,DNA損傷による転写抑制を調節する
Midori Shimada1, Hiroyuki Niida, Doaa H Zineldeen
1Department of Cell Biology and Biochemistry, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Cell
|February 5, 2008
まとめ
DNAの損傷はヒストンH3トレオニン11のリン酸化を急速に低下させ,サイクリンB1.1のような遺伝子を抑制します. これは,クロマチンからChk1の解離を伴い,ヒストンのアセチル化と遺伝子転写を減少させます.
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
- エピジェネティクス エピジェネティクス
背景:
- DNAの損傷は,トランスクリプションの活性化と抑制を含む複雑な遺伝子発現変化を誘発する.
- DNA損傷誘発の転写抑制の基礎となるメカニズムは,活性化経路と比較して,まだ十分に理解されていません.
研究 の 目的:
- DNA損傷誘発の転写抑制におけるヒストン変異の役割を調査する.
- DNA損傷後の遺伝子発現の調節におけるChk1キナーゼの関与を明らかにする.
主な方法:
- DNA損傷後のヒストンH3トレオニン11 (H3-T11) のリン酸化ダイナミクスの分析.
- Chk1キナーゼ活性とクロマチンの関連性の評価.
- ヒストンのアセチル化と転写因子の結合を標的遺伝子プロモーターで評価するためのクロマチンの免疫プレシピテーション.
主要な成果:
- DNAの損傷はH3-T11のリン酸化を急速に減少させ,サイクリンB1やcdk1.1などの遺伝子の抑制と相関する.
- H3-T11のリン酸化は細胞周期に依存し,Chk1.1によって調節される.
- Chk1はDNA損傷時にクロマチンから解離し,H3-T11のリン酸化が低下し,ヒストンアセチルトランスファーゼのGCN5結合が低下する.
- H3-T11リン酸化の喪失は,標的遺伝子プロモーターにおけるH3-K9アセチル化の減少と関連しています.
結論:
- Chk1はヒストンキナーゼとして作用し,DNA損傷による転写抑制を媒介する.
- このメカニズムは,Chk1-依存のH3-T11のリン酸化と,その後のヒストンアセチル化の喪失を含む.
- この研究は,DNA損傷への反応として遺伝子発現の表遺伝的調節のための新しい経路を明らかにしています.
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