线性循环蛋白对Cdc6的酸化依赖的结合有助于控制DNA复制
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
概括
循环素依赖激酶 (CDKs) 通过与DNA复制中的关键蛋白Cdc6结合来阻止DNA重复制. 这种由环林Clb2介导的相互作用抑制了细胞分裂期间的复制前复合组合.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 循环素依赖激酶 (CDK) 调节细胞循环,包括DNA复制.
- CDKs在S,G2和M阶段阻止了DNA复制起源的重新激活.
- 通过各种机制,CDKs抑制了复制前复合 (pre-RC) 组件.
研究的目的:
- 为了研究 mitotic CDK Clb2/Cdc28 抑制 Cdc6.6 的机制.
- 为了确定Clb2与Cdc6的结合是否可以防止RC前组合和在体内重复复制.
- 探索酸化在CDK-Cdc6相互作用中的作用.
主要方法:
- 在Saccharomyces cerevisiae中的酵母遗传学和生物化学.
- 通过使用重组蛋白和合成来分析Clb2/Cdc28与Cdc6的结合.
- 研究酸化对CDK结合Cdc6NTD的影响.
主要成果:
- 线性CDK Clb2/Cdc28直接与Cdc6.6的氨基末端域 (NTD) 结合.
- 这种Clb2-Cdc6相互作用阻止了RC前组合,有助于防止DNA重复复制.
- CDK与Cdc6 NTD结合需要在CDK共识站点上进行酸化.
- 人类的CDK也与酸化NTD结合,这表明一种保存机制.
结论:
- 线性CDKClb2与化Cdc6NTD的直接结合是防止DNA重复制的一个关键机制.
- 对基质的酸化依赖性环林结合可能是CDK向的一般机制.
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相关概念视频
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...