関連する実験動画
Updated: May 13, 2026
07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 30, 2010
イントラ-SフェーズチェックポイントはDna2をターゲットにして,停滞した複製フォークが逆転するのを防止します
Jiazhi Hu1, Lei Sun, Fenfen Shen
1The National Laboratory of Protein Engineering and Plant Genetic Engineering, The College of Life Sciences, Peking University, Beijing, China.
Cell
|June 12, 2012
まとめ
Cds1キナーゼはDna2を標的にして,複製ストレス中に複製フォークの逆転を防ぐ. このメカニズムは,停止したフォークを安定させ,ゲノムの安定性を維持し,細胞死を防ぐ.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- 複製フォークは,ストレス下では停止し,安定化と再起動のためのチェックポイントを必要とします.
- S相内チェックポイントの欠乏は,フォーク崩壊と細胞死につながる.
研究 の 目的:
- 停滞した複製フォークの安定化におけるCds1エフェクターキナーゼとDna2の役割を調査する.
- 複製フォークの逆転をDna2が防ぐメカニズムを解明する.
主な方法:
- 分裂酵母をモデル生物として利用した.
- Dna2と停滞した複製フォークの関連性をin vivoおよびin vitroで調査した.
- フォークの逆転を防ぐために必要なDna2リン酸化とヌクレアース活性を評価した.
- モデルの複製フォークでDna2による後退した新生鎖の割れ目を分析した.
主要な成果:
- Cds1 (Chk2) は,S220上のDna2を標的にして,停止した複製フォークとの関連を調節します.
- S220におけるDna2のリン酸化とその核酵素活性性は,複製フォークの逆転を防ぐために不可欠である.
- Dna2は,フォーク回帰の先駆けである,後退した先導性または後退性鎖を効率的に分割します.
- Dna2の分裂活動はフォークの逆転を防止し,停止したフォークを安定させます.
結論:
- 逆行した新生鎖のDna2分裂は,複製フォークの逆転を防ぐための重要なメカニズムです.
- このプロセスは,停滞したフォークを安定させ,複製ストレス中にゲノム安定に貢献します.
- Cds1-Dna2経路は,遺伝子毒性ストレス下での複製の完全性を維持するために重要である.
関連する概念動画
01:02The DNA Replication Fork
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
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...
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
01:02The DNA Replication Fork
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
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...
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...