ミトシクリンがCdc6にリン酸化に依存して結合することは,DNA複製制御に寄与する
Satoru Mimura1, Takashi Seki, Seiji Tanaka
1Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, UK.
Nature
|October 22, 2004
まとめ
サイクリン依存キナーゼ (CDK) は,DNA複製の鍵となるタンパク質であるCdc6に結合することで,DNA再複製を防ぐ. この相互作用は,サイクリンClb2によって媒介され,細胞分裂中の複製前の複合体の組み立てを阻害する.
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.
- バイオケミストリー バイオケミストリー
背景:
- サイクリン依存キナーゼ (CDK) は,DNA複製を含む細胞サイクルを調節する.
- CDKは,S,G2,M段階のDNA複製原点の再活性化を防止する.
- CDKsは,様々なメカニズムを通じて,複製前複合体 (pre-RC) 構成要素を阻害する.
研究 の 目的:
- ミトスのCDK Clb2/Cdc28がCdc6.6を抑制するメカニズムを調査する.
- Cdc6へのClb2結合が,pre-RCアセンブリと再複製をin vivoで防ぐかどうかを決定する.
- CDK-Cdc6相互作用におけるリン酸化の役割を調査する.
主な方法:
- 酵母遺伝学と生化学は,Saccharomyces cerevisiaeに含まれています.
- 再結合タンパク質と合成ペプチドを用いてCdc6に結合するClb2/Cdc28の分析.
- Cdc6 NTDに結合するCDKに対するリン酸化の効果を調査する.
主要な成果:
- ミトスのCDKClb2/Cdc28は,Cdc6.6のアミノ末端領域 (NTD) に直接結合する.
- このClb2-Cdc6相互作用は,RC前アセンブリを防止し,DNA再複製の予防に寄与します.
- CDKがCdc6 NTDに結合するには,CDKコンセンサスサイトでのリン酸化が必要です.
- また,ヒトのCDKは,酸化NTDペプチドと結合し,保存されたメカニズムを示唆する.
結論:
- ミトスのCDK Clb2がリン酸化Cdc6 NTDに直接結合することは,DNA再複製を防ぐための重要なメカニズムです.
- 基板への酸化依存性サイクリン結合は,CDKターゲティングの一般的なメカニズムである可能性があります.
さらに関連する動画
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Published on: December 5, 2017
12:26Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
関連する概念動画
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...