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ドロソフィラp53は,ダメージレスポンスの要素をリッパー位置に結合する
M H Brodsky1, W Nordstrom, G Tsang
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA.
Cell
|April 25, 2000
まとめ
研究者らは,DNA損傷に対する細胞の反応を調節するドロソフィラp53のホモログを特定した. この遺伝子は,プロアポプトシス遺伝子の刈り取りを直接標的にし,発達中の組織における放射線誘発のアポトシスに影響を与えます.
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
- 発達生物学 発達生物学とは
背景:
- 腫瘍抑制物質p53は,DNA損傷に対する細胞の反応に不可欠ですが,その転写標的はほとんど不明のままです.
- p53の規制ネットワークを理解することは,DNA損傷反応経路の解読に不可欠です.
研究 の 目的:
- ドロソフィラ p53 ホモログを特定し,特徴づけること.
- DNA損傷後の転写調節とアポトーシスにおけるドロソフィラp53の役割を調査する.
- プロアポプトシス遺伝子のリーパーが,ドロソフィラp53.3の直接的な転写標的であるかどうかを判断する.
主な方法:
- ドロソフィラ p53 ホモログのクローニングと特徴付け.
- 酵母と培養細胞のp53結合部位を用いた転写活性化に関する試験.
- 主要負のp53形態の機能分析 in vivo.
- リーパー遺伝子のシス調節領域の特定と分析.
- 放射線によって誘発された遺伝子発現のインビオ研究.
主要な成果:
- 人間のp53結合部位からの転写を活性化できる機能的なDrosophila p53ホモログが特定されました.
- 支配的陰性ドロソフィラp53がトランザクティベーションを阻害し,放射線誘発のアポトーシスを引き起こした.
- プロアポプトティック・ゲン・リーパーには,p53結合部位を持つ放射線誘導性増強剤があります.
- ドロソフィラp53は,酵母体と体内のリパーエンハンスターから直接トランスクリプションを活性化します.
結論:
- ドロソフィラp53は,DNA損傷への反応として,転写レギュレータとして作用します.
- リーパー遺伝子は,ドロソフィラp53.3の直接的な転写標的である.
- この研究は,哺乳類で保存されているドロソフィラのDNA損傷反応経路の重要な構成要素を明らかにしています.
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