DNA塩基Jであるグルコシル化ヒドロキシメチルウラシルは,ライシュマニアの転写読読を阻害する

Henri G A M van Luenen¹, Carol Farris, Sabrina Jan

¹Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Cell

|September 4, 2012

まとめ

塩基Jは,改変されたDNA塩基であり,リーシュマニアの適切な転写終結に不可欠です. 特に内部部位でのその欠如は,大規模な読み込みを引き起こし,細胞死につながります.

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
寄生虫学とは,寄生虫学である.

背景:

DNA塩基J (β-D-glucosyl-hydroxymethyluracil) は,トライパノソームとリーシュマニアに見られる修飾されたチミンである.
主にテロメア重複に配置されているが,内部ベースJの機能は以前は不明であった.

研究の目的:

レイシュマニアにおける染色体内基Jの位置と機能を調査する.
J塩基生物合成におけるJ結合タンパク質2 (JBP2) の役割とその転写への影響を決定する.

主な方法:

リーシュマニアにおけるJBP2の遺伝子ノックアウトにより,J基のレベルを低下させる.
BrdUを含む媒介でJBP2ノックアウト細胞を培養する.
RNAポリメラーゼIIの終末部位とトランスクリプションの読み込みの分析.

主要な成果:

ほとんどの非テロメア塩基Jは,内部RNAポリメラーゼII終末部位に位置しています.
JBP2のノックアウトにより,テロメアと内部ベースJの両方が著しく減少しました.
内部塩基Jの喪失は,終末部位で100kBを超える大規模な転写読読をもたらした.

結論:

塩基Jは,効率的なRNAポリメラーゼII転写終結に不可欠である.
内部塩基Jの欠如は,ライシュマニアで致命的な転写読読につながる.

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