AID酵素が誘発した,線維芽細胞の活性的に転写される遺伝子のハイパーミューテーション
Kiyotsugu Yoshikawa1, Il-Mi Okazaki, Tomonori Eto
1Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Science (New York, N.Y.)
|June 18, 2002
まとめ
アクティベーション誘発型シチジンデアミナーゼ (AID) 単独では,線維芽細胞内の転写された遺伝子の遺伝子ハイパーミューテーションを誘発することができます. これは,AIDが様々な細胞タイプにおける体性高変異 (SHM) 生成に十分であることを示唆しています.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 活性化誘発型シチジンデアミナーゼ (AID) は,免疫グロブリン遺伝子の多様化に不可欠です.
- AIDは,体性高変異 (SHM),クラススイッチ再結合,遺伝子変換に不可欠です.
研究 の 目的:
- AID単独で非B細胞のハイパーミューテーションを誘発するのに十分であるかどうかを調査する.
- 積極的に転写された遺伝子の突然変異を生成するAIDの役割を決定する.
主な方法:
- NIH 3T3 ネズミの線維芽細胞におけるAIDの胎外発現.
- 変異の頻度と分布を評価するために人工GFPレポーター遺伝子を利用しました.
- 変異の頻度は,標的遺伝子転写のレベルと相関しています.
主要な成果:
- エクトピックAID発現は,線維芽細胞内のGFP基板におけるハイパーミューテーションを誘発した.
- 変異の頻度は,標的遺伝子の転写レベルと直接相関しています.
- 線維芽細胞の変異分布は,SHM中にBリンパ球で観察されたものと同じでした.
結論:
- AIDは,線維芽細胞の活性的に転写された遺伝子の体性高変異 (SHM) を生成するのに十分です.
- AID活動に必要なコファクターは,ネズミの線維芽細胞に存在します.
- これらの発見は,異なる細胞タイプにおけるSHMの共通の分子メカニズムを示唆しています.
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