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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
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ヒストンH1カップルの開始とDNA損傷後のユビキチン信号の増幅
Tina Thorslund1, Anita Ripplinger1, Saskia Hoffmann1
1Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Nature
|October 28, 2015
まとめ
ヒストンH1は,DNA二重鎖断裂シグナル伝達におけるRNF8-UBC13の主要な標的である. この発見は,RNF8とUBC13がRNF168を修復部位に採用し,ゲノムの安定性を維持する方法を説明しています.
科学分野:
- 分子生物学
- 遺伝学
- 生物化学
背景:
- DNAの二重鎖の断裂 (DSB) は重要なDNAの損傷です.
- DSBの近くのクロマチンのユビキティレーションはDNA修復因子を誘発する.
- RNF8,RNF168,UBC13は,DSB応答における主要なE3/E2ユビキチン結合体である.
研究 の 目的:
- RNF8 と UBC13 が RNF168 と DSB サイトへの下流因子を誘発する役割を明らかにする.
- DSBシグナル伝達におけるRNF8とK63関連ユビキティレーションの重要な基質を特定する.
主な方法:
- ヒトの細胞のDSB部位における全域的発生を調査した.
- タンパク質とユビキチンの相互作用を特定するために生化学的測定を用いた.
- ヒストンH1発現がDNA修復因子に与える影響を評価した.
主要な成果:
- RNF8とUBC13は,主としてコアヒストンではなくヒストンH1を標的にして,DSBのサイトでK63関連ユビキチレーションを媒介する.
- RNF168 UDM1モジュールは,K63-ubiquitylated histone H1を認識し,RNF168がDSBに採用されたことを説明します.
- ヒストンH1濃度の低下は,ユビキチン結合体と修復因子の蓄積を阻害する.
結論:
- ヒストンH1は,DSBシグナル伝達におけるRNF8-UBC13の主な標的である.
- ヒストンH1の翻訳後の改変は,ゲノム安定性因子の認識マークとして機能する.
- これはヒストンコードの概念を拡張し,DNA修復経路にリンクヒストンの修正を含みます.
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