TIP60ヒストンアセチラゼ複合体のDNA修復とアポトーシスへの関与

T Ikura¹, V V Ogryzko, M Grigoriev

¹Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

Cell

|August 31, 2000

まとめ

TIP60ヒストンアセチラゼ複合体は,クロマチンを改変するだけでなく,DNA修復とアポトーシスに不可欠です. アセチラゼの活性を損なう突然変異は,二重鎖破裂修復とアポプトシグナル伝達を妨げます.

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
バイオケミストリーバイオケミストリー

背景:

ヒストンアセチラゼは,遺伝子転写を調節する重要な染色体変形剤である.
TIP60タンパク質は,これらのプロセスに関与するヒストンアセチラゼとして知られています.

研究の目的:

ヒストンアセチラゼ,特にTIP60複合体の新しい機能を調査する.
細胞プロセスにおけるTIP60の酵素活動の役割を明らかにする.

主な方法:

TIP60タンパク質複合体の浄化と特徴付け.
ATPase,DNAヘリカーゼ,DNA結合を含むTIP60の複合的な活動を評価する.
変異したTIP60 (ヒストンアセチラゼ活性がない) が,子宮外発現によるDNA修復とアポトーシスに及ぼす影響を分析した.

主要な成果:

TIP60複合体は,ヒストンアセチラゼの機能に加えて,ATPアゼ,DNAヘリカーゼ,DNA結合活性を示す.
ヒストンアセチラゼ活性に欠けているTIP60変異体の子宮外発現は,二重鎖DNA破裂修復の障害をもたらした.
これらの変異体を発現する細胞は,アポプトティック能力の喪失を示し,DNA損傷シグナリングの失敗を示した.

結論:

TIP60を含む複合体は,DNA修復経路において重要な役割を果たしています.
TIP60のヒストンアセチラゼ活動は,DNA損傷に対する適切なアポトーシスシグナル伝達に不可欠です.

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