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ヒトコヘシンによるDNAループエクストルーション
Iain F Davidson1, Benedikt Bauer1, Daniela Goetz1
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Science (New York, N.Y.)
|November 23, 2019
まとめ
人間のコヘシン複合体は DNAをループに活かして 重要なクロマチンの構造を形成します このプロセスは,コヘシンに依存しています.
科学分野:
- 分子生物学
- ゲノミクス
- 生物化学
背景:
- ユカリオットのゲノムはループとトポロジカルな関連ドメインに折り畳み,遺伝子調節と再結合に影響を与えます.
- これらの構造は,DNAを捕まえるATPase複合体であるコヘシンに依存し,挤出によってループを形成することが提案されています.
- コンデンシンがミトーシスでループエクストルーションを示す一方で,コヘシンの活動は未確認のままである.
研究 の 目的:
- コヘシンが DNAのループを形成するかどうかを調査する.
- コヘシン媒介のループ形成のメカニズムと要件を明らかにする.
主な方法:
- ヒトコヘシン複合体の生化学的再構成
- 単一のコヘシン複合体によるDNAループ形成のリアルタイム観測.
- ATPase活性,NIPBL-MAU2,およびトポロジカル・エントラップメントへの依存を決定する試験.
主要な成果:
- 単一のヒトコヘシン複合体は,毎秒2.1キロベースペアまでの速度で DNAループをエクスプロードします.
- ループの形成と維持には,コヘシンのATP酶活性とNIPBL-MAU2因子が必要です.
- コヘシンによるDNAのトポロジカル・エントラップメントはループ・エクストルーションには必要ありません.
- コヘシンとNIPBL-MAU2は,挤出ループの底部に定着し,挤出におけるその役割を確認します.
結論:
- コヘシンとNIPBL-MAU2は,インターフェーズ中にループにDNAを挤出できる活性ホロ酵素を形成する.
- トポロジカル・エントラップメントとは無関係なこのループ・エクストルーション・メカニズムは,クロマチン組織にとって根本的なものである.
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