サイクリン依存キナーゼは,複数のメカニズムを通じてDNAの再複製を防止します
V Q Nguyen1, C Co, J J Li
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0414, USA.
Nature
|June 29, 2001
まとめ
DNA複製の再始動を防ぐことは,細胞サイクル制御にとって極めて重要です. 酵母体では,B型サイクリン依存キナーゼ (CDK) は,再複製を阻害する3つのメカニズムを使用して,ゲノム安定性を確保します.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 細胞サイクル1回に1度,忠実なゲノム複製は,遺伝的安定性にとって不可欠である.
- ユカリオットDNAの複製は複数の起源で開始され,同じ細胞サイクル内で再始動を防ぐ必要があります.
- サイクリン依存キナーゼ (CDK) は,複製の再始動を阻害する役割を果たすことが知られているが,正確なメカニズムは未だに曖昧である.
研究 の 目的:
- B型サイクリン依存キナーゼ (CDK) がSaccharomyces cerevisiaeにおけるDNA複製の再始動を防ぐメカニズムを解明する.
- CDKsによって調節される個々の阻害経路の機能的重要性を決定する.
主な方法:
- 酵母における複製の再始動を防止するB型CDKの役割を調査した.
- 起源認識複合体 (ORC) のリン酸化,Cdc6の活性,およびMcm2-7複合体の局所化に対するCDK活動の影響を分析した.
- G2/M相細胞におけるDNA複製に対するこれらの調節経路の破壊の結果を評価した.
主要な成果:
- Saccharomyces cerevisiaeのB型CDKは,複製の再始動を抑制するために,複数の重複するメカニズムを採用しています.
- これらのメカニズムには,起源認識複合体 (ORC) のリン酸化,Cdc6活動のダウンレギュレーション,Mcm2-7複合体の核排除が含まれます.
- 3つの抑制経路が同時に破壊されたときのみ,複製の起源がG2/M細胞のDNA複製を再始動します.
結論:
- B型CDKは,細胞サイクル毎に1回だけのDNA複製を確実にするために,多角的抑制戦略を使用します.
- 特定された規制メカニズム (ORCのリン酸化,Cdc6のダウンレギュレーション,Mcm2-7の排除) のそれぞれが,再起動を防止する上で機能的に重要である.
- これらの発見は,真核細胞がDNA複製を厳格に制御することによって,ゲノム安定性を維持する方法の包括的な理解を提供します.
関連する概念動画
DNA Topoisomerases
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. Type I...
Types and Mechanism of action
Topoisomerases are divided into two main types. Type I...
DNA 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...
Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Restarting 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...
Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
DNA 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...


