实验室中依赖于真核生物起源的DNA复制揭示了DDK和S-CDK激酶的顺序作用
Ryan C Heller1, Sukhyun Kang, Wendy M Lam
1Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Cell
|July 7, 2011
概括
细胞DNA复制需要精确的时间. 在S相环素依赖激酶 (S-CDK) 之前,Dbf4依赖的Cdc7激酶 (DDK) 启动了原始招募,然后使复制体组装和DNA合成成为可能.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞DNA复制是一个复杂的过程.
- 螺旋酶加载,激活和复合体组装的时间分离至关重要.
- 了解复制启动的调节是细胞周期控制的关键.
研究的目的:
- 为了研究真核细胞DNA复制启动的控制机制.
- 阐明Dbf4-依赖的Cdc7激酶 (DDK) 和S相环林依赖激酶 (S-CDK) 在复制中的不同作用.
- 定义起源发射和重复组合过程中的事件序列.
主要方法:
- 采用了体外试验测试以确定真核细胞起源依赖的复制启动.
- 进行了体内研究,以观察复制动态.
- 研究了Sld3,Cdc45,GINS和DNA聚合酶等关键蛋白质的招募.
主要成果:
- 需要DDK,而不是S-CDK,在螺旋酶加载后对Sld3和Cdc45的初始来源征集.
- 在体内,DDK在S-CDK激活之前驱动Cdc45的早期发射起源招募.
- 激活S-CDK有助于GINS和剩余的复杂组的招募.
- 滞后链DNA聚合酶的招募取决于Mcm10和DNA解,与领先链的招募不同.
结论:
- DDK和S-CDK在调节酶激活和复合体组合方面发挥着不同的,顺序的作用.
- 支持一个模型,在源DNA解和RNA原料合成之前,招募领先链DNA聚合酶.
- 这项研究澄清了精确DNA复制启动所必需的事件的时间顺序.
相关概念视频
02:31Replication in Eukaryotes
Overview
02:31Replication in Eukaryotes
Overview
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.
01:29Replication in Eukaryotes
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
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.
01:29Replication in Eukaryotes
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...