窒素中心のピュリン基からのDNAの痕跡のないタンデム損傷形成
Liwei Zheng1, Marc M Greenberg1
1Department of Chemistry , Johns Hopkins University , 3400 North Charles Street , Baltimore , Maryland 21218 , United States.
Journal of the American Chemical Society
|May 9, 2018
まとめ
窒素を中心としたラジカルは 痕跡のない経路で DNAのダンドム病変を起こします このメカニズムは,2'-デオキシアデノシン-N6-イルラジカルを含み,ガンマ放射分解の際に重大なDNA損傷を生成します.
科学分野:
- DNA 損傷と修復
- 放射線化学
- 核酸ラジカル化学
背景:
- 窒素を中心とした核酸根は,放射解離と酸化物質によるDNA損傷における重要な中間物質である.
- 病変形成におけるそれらの正確な反応性と役割は,まだ完全に理解されていません.
研究 の 目的:
- 独立して生成された2-デオキシアデノシン-N6-イル基 (dA•) の反応性を調査する.
- dA•がタンデムDNAの損傷を起こすメカニズムを解明する.
主な方法:
- dA• と T• の独立生成
- 液体染色体-タンデム質量スペクトロメトリー (LC-MS/MS)
- イソトープの標識と化学反応の実験
主要な成果:
- dA•は隣接するチミジンから水素を抽出し,T•を形成することによって,O2依存のタンデム病変を開始する.
- このプロセスは,特定のシーケンスで27%以上の収量を持つ5 -OxodGuo-fdUタンデムレシオンを生成します.
- dA•は水素抽出過程でdAに修復され,その関与の痕跡がないようにします.
結論:
- 2 -デオキシアデノシン-N6-イルラジカルは,タンデムDNA損傷形成のための新しい,痕跡のない経路を開始します.
- このメカニズムは,γ放射分解の際にDNAの損傷に大きく寄与する.
- この発見は,核酸の窒素を中心とした基に広く適用できる.
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