ユカリオットの複製性DNAヘリケーゼによって,遅滞する鎖の道路障壁を選択的にバイパスする
Yu V Fu1, Hasan Yardimci, David T Long
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|September 20, 2011
まとめ
CMGヘリケーゼは"ステリック排除"メカニズムを使用してDNAを解き放ち,単一のDNA鎖に沿って転位します. このプロセスは,複製中に二重鎖から単一鎖のDNA結合への改造を伴う.
科学分野:
- 分子生物学は分子生物学である.
- DNAレプリケーション DNA複製
- バイオケミストリー バイオケミストリー
背景:
- CMG (Cdc45-MCM-GINS) 複合体は,主として真核生物の複製性DNAヘリカーゼである.
- そのDNA解き放つメカニズムは,競合するモデルでは,まだ完全に理解されていません.
- モデルでは,CMGが単一鎖DNA (ssDNA) または二鎖DNA (dsDNA) のいずれかを包囲することを提案しています.
研究 の 目的:
- CMGヘリカーゼのDNA転位メカニズムを解明する.
- CMGにおけるssDNAとdsDNAの転位モデルを区別する.
- CMGの機能における鎖特異的なDNAの障害の役割を調査する.
主な方法:
- レプリソームのダイナミクスを研究するために,Xenopusの卵エキスを利用しました.
- 複製機構と対峙するために,鎖特異のDNAのブロックを導入した.
- 定義されたDNA阻害に対する反応として,レプリソームの停滞とバイパスが観察されました.
主要な成果:
- レプリソームは,先行する対後退するストランドテンプレートで,大きな道路障壁の差分バイパスを示した.
- 遅滞するストランドのテンプレートの障害物は,先行するストランドの障害物よりも簡単に回避されました.
- これらの発見は,CMGが3'から5' ssDNAトランスロカゼとして機能することを示している.
結論:
- CMGヘリケーゼは,ssDNAトランスロケーションと一致する"ステリック排除"メカニズムを通じてDNAを解き放つ.
- 複製の開始には,MCM2-7がdsDNAを包囲し,S相ではssDNA結合モードに改造される.
- この改造は,DNA複製中のプロセス性ssDNAトランスロカゼとしてのCMGの機能に極めて重要です.
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