对Sld2和Sld3的CDK-依赖酸化启动了在芽酵母中DNA复制的过程
Seiji Tanaka1, Toshiko Umemori, Kazuyuki Hirai
1Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
Nature
|December 15, 2006
概括
循环素依赖激酶 (CDK) 通过控制蛋白相互作用来调节DNA复制的启动. 这项研究揭示了CDK独立途径如何绕过重要的CDK基质,为细胞周期控制提供了新的见解.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 循环素依赖激酶 (CDK) 是真核细胞循环的关键调节者.
- 在S阶段,CDKs在启动染色体DNA复制中发挥着至关重要的作用.
- 在DNA复制中CDKs的确切功能仍然不完全理解.
研究的目的:
- 阐明CDK基质在启动染色体DNA复制中的作用.
- 调查绕过DNA复制中CDK活性要求的机制.
- 了解CDK依赖酸化如何调节DNA复制所必需的蛋白质相互作用.
主要方法:
- 作为一个模型系统,利用了芽酵母 (Saccharomyces cerevisiae).
- 采用基因操纵,包括特定的等位基因 (JET1) 和基因拷贝数变异 (高拷贝DPB11).
- 使用模仿突变体 (Sld2-11D) 研究了蛋白质与蛋白质相互作用和酸化依赖的结合事件.
主要成果:
- 确定了CDC45 (JET1等位基因) 和DPB11作为与Sld2-11D结合时赋予CDK独立DNA复制的因素.
- 证明CDK依赖的Sld3化对于产生DPb11结合点至关重要.
- 表明JET1突变和高副本DPB11绕过了Sld3酸化的需要.
- 提出了一个模型,其中Dpb11桥梁酸化Sld2和Sld3,促进复制蛋白质复合体的形成.
结论:
- CDKs通过调节含有BRCT域的蛋白质及其酸化伙伴之间的相互作用来调节DNA复制的启动.
- 这些发现突出了细胞循环调节的保存机制,可能适用于更高的真核生物.
- 确定了在DNA复制启动过程中绕过正规CDK控制的新途径.
相关概念视频
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...
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...
02:38S-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.
02:36DNA 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...
02:38S-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.