サイクリン依存キナーゼによるSld2およびSld3のリン酸化は,芽生えた酵母におけるDNA複製を促進する
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
まとめ
サイクリン依存キナーゼ (CDK) はDNA複製を開始する. S-CDKsによるSld2およびSld3タンパク質のリン酸化は,このプロセスにとって不可欠であり,DNA複製に必要な最小のCDK標的を明らかにします.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 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複製の開始を含む,重要な細胞サイクルイベントを調節する.
- Sld3タンパク質は芽生えた酵母におけるS相CDK (S-CDK) の主要標的である.
- BRCTの繰り返しを含むDPb11タンパク質は,Sld3.3と相互作用する.
研究 の 目的:
- Sld3.3上のS-CDKリン酸化部位の機能的重要性を調査する.
- リン酸化Sld3とDPb11の相互作用を解明する.
- DNA複製に不可欠なS-CDK標的の最小セットを決定する.
主な方法:
- Sld3.3のS-CDKリン酸化部位を特定するためのサイト指向型変異.
- Sld3-Dpb11融合コンストラクタを作成するための酵母遺伝学.
- 様々な変異酵母菌株におけるDNA複製開始の分析.
主要な成果:
- Sld3の2つのS-CDKリン酸化部位は,DNA複製に不可欠である.
- リン酸化Sld3は,Dpb11.0のBRCTリピートに結合する.
- Sld3-Dpb11融合は,Sld3のリン酸化とDpb11のBRCTの繰り返しを必要としない.
- フォスフォを模倣するSld2変異体との融合の共同発現は,S-CDKなしで複製を促進します.
- Cdc7キナーゼサブユニットDbf4の発現は,Sld2とSld3バイパスとともに,G1-CDK欠乏細胞の複製のために必要である.
結論:
- Sld2とSld3は,DNA複製の開始に必要な最小のS-CDK基板である.
- リン酸化Sld3とDPb11の相互作用は,複製に不可欠である.
- この研究は,酵母DNA複製を促進するG1-およびS-CDKの役割を明らかにしています.
関連する概念動画
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...