核孔に関連したSUMO依存性ユビキチンリガゼへのDNA損傷の機能的ターゲティング
Shigeki Nagai1, Karine Dubrana, Monika Tsai-Pflugfelder
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Science (New York, N.Y.)
|October 25, 2008
まとめ
核の組織はゲノムの安定性に影響を与えます. 損傷したDNAは,SUMO依存リガゼ経路によって Slx5/Slx8 と Nup84.4 を含む核毛孔に修復のために集められる.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 核組織は遺伝子発現に影響しますが,ゲノム安定性におけるその役割はあまり理解されていません.
- Slx5/Slx8複合体は,DNA修復に関与する小さなユビキチン類似変容体 (SUMO) に依存したユビキチンリガゼである.
- 核毛孔は,核と細胞質の間の接点にある重要な構造です.
研究 の 目的:
- ゲノムの安定性を維持する核組織の役割を調査する.
- 核孔複合体とDNA修復因子の機能的関係を調査する.
- 核の周辺でDNAの損傷を制御するメカニズムを解明する.
主な方法:
- DNA修復因子間の機能的関係を特定するために,エピスタシスミニアレイ分析 (E-MAP) を行う.
- 損傷したDNAのダイナミックな再生を観察するためのリアルタイム画像処理.
- DNAとタンパク質の相互作用を確認するためのクロマチンの免疫プレシピテーション (ChIP).
- タンパク質複合体間の物理的な相互作用を確認するための生化学的分析.
主要な成果:
- 核毛孔サブコンプレックスとSlx5/Slx8 SUMO依存型ユビキチンリガゼの間の機能的リンクが特定されました.
- 核毛孔複合体とSlx5/Slx8.8との間の物理的な相互作用が確認されました.
- 損傷したDNAが核毛穴に安定して集まるのがリアルタイムで観察されました.
- 核孔へのDNAの移動には,Nup84複合体とMec1/Tel1キナーゼが必要です.
- 核周辺のドナー部位を結合させることで,Slx8とNup84に依存した方法で自発的な遺伝子変換が促進されます.
結論:
- 核毛孔は,DNA修復を促進することによって,ゲノムの安定性において重要な役割を果たします.
- DNA鎖の断裂は,保存されたSUMO依存のE3リガース経路を通じて処理するために核の毛穴に導かれます.
- Slx5/Slx8リガゼとNup84複合体は,この核孔関連DNA修復機構の重要な構成要素である.
関連する概念動画
01:08Nucleotide Excision Repair
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01:38Nucleotide Excision Repair
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Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
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02:10Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
02:36DNA Damage can Stall the Cell Cycle
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02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...