損傷したtRNAの核輸出は,DNA損傷と細胞サイクルチェックポイントを結びつける
Ata Ghavidel1, Thomas Kislinger, Oxana Pogoutse
1Ontario Cancer Institute, Division of Signaling Biology, Toronto, Ontario M5G-1L7, Canada. aghavide@uhnres.utoronto.ca
Cell
|November 30, 2007
まとめ
DNAの損傷は,シグナル伝達経路によって媒介される酵母における未結合転移RNA (tRNA) の核蓄積を誘発する. これは,細胞サイクル停止とゲノム整合性に影響を及ぼします.
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:
- 細胞は,遺伝子毒性ストレス下でのゲノム整合性を維持するために複雑な反応を活性化します.
- トランスファーRNA (tRNA) バイオゲネシスと核サイトプラズマの密輸は,タンパク質合成と細胞機能にとって極めて重要です.
研究 の 目的:
- DNAダメージに対する酵母反応における未配合のtRNA蓄積の役割を調査する.
- tRNAの核輸出を調節する分子機構とその細胞サイクル進行への影響を解明する.
主な方法:
- 利用された酵母Saccharomyces cerevisiaeのモデルシステム.
- MEC1およびRAD53.3を含むDNA損傷応答経路が調査されています.
- 分析されたtRNA核細胞質の密輸とGcn4転写因子の活性化.
主要な成果:
- 酵母菌のDNA損傷後の酵母核で,未配合のtRNAの急速な蓄積が観察されました.
- MEC1-およびRAD53-依存による,イントロンを含むtRNAの核輸出の抑制が実証されています.
- 核未結合のtRNAがGcn4を活性化し,Cln2の蓄積を遅らせることによってG1細胞サイクル停止に貢献することを示した.
結論:
- 規制された核サイトプラズマのtRNAの密輸は,DNA損傷への不可欠な適応です.
- tRNAの密輸,タンパク質合成,チェックポイントの実行の間のクロストラックは,tRNAの生体生成と細胞サイクル進行を機能的に結びつける.
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