通过循环素依赖性激酶对Sld2和Sld3的酸化促进了芽生长酵母中的DNA复制
Philip Zegerman1, John F X Diffley
1Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
Nature
|December 15, 2006
概括
循环素依赖激酶 (CDK) 启动DNA复制. 这一过程中,S-CDKs对Sld2和Sld3蛋白质的酸化是必不可少的,它揭示了DNA复制所需的最小CDK标.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 循环素依赖激酶 (CDK) 调节关键细胞周期事件,包括启动DNA复制.
- 在芽酵母中,Sld3蛋白是S相CDK (S-CDK) 的关键标.
- 含有BRCT重复的DPb11蛋白与Sld3.3相互作用.
研究的目的:
- 调查Sld3.3上的S-CDK化位点的功能意义.
- 为了阐明化Sld3和DPb11之间的相互作用.
- 确定DNA复制所必需的S-CDK目标的最小集合.
主要方法:
- 位点定向突变发生,以确定Sld3.3上的S-CDK酸化位点.
- 酵母基因创造Sld3-Dpb11的融合结构.
- 在各种突变酵母菌株中对DNA复制启动的分析.
主要成果:
- 在Sld3上有两个S-CDK酸化点,对于DNA复制至关重要.
- 化Sld3与DPb11的BRCT重复结合.
- 一个Sld3-Dpb11的融合绕过了Sld3酸化和DPb11的BRCT重复的需要.
- 融合与模仿素的Sld2突变体的共同表达促进了没有S-CDK的复制.
- 在G1-CDK缺陷细胞中复制需要Cdc7激酶子单元Dbf4的表达,以及Sld2和Sld3绕道.
结论:
- Sld2和Sld3是DNA复制启动所需的最小的S-CDK基质.
- 化Sld3和DPb11之间的相互作用对于复制至关重要.
- 这项研究阐明了G1-和S-CDKs在促进酵母DNA复制中的作用.
相关概念视频
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.
02:38S-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.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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.
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
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...