作为重组修复的调节机制,BRCA2的CDK依赖酸化是重组修复的调节机制
Fumiko Esashi1, Nicole Christ, Julian Gannon
1Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
Nature
|April 1, 2005
概括
通过损害DNA修复,BRCA2突变增加了癌症风险. 在BRCA2中,血清蛋白3291酸化起到关键作用,调节RAD51相互作用和DNA修复,提供了新的癌症见解.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 遗传的BRCA2突变与早期发病的乳腺癌有关.
- 瘤发生与通过同源重组的DNA双链断裂修复的缺陷有关.
研究的目的:
- 研究BRCA2酸化在调节DNA修复中的作用.
- 了解BRCA2与RAD51的C端相互作用是如何控制的.
主要方法:
- 研究了BRCA2C末端区域中血清3291 (S3291) 的酸化.
- 评估了S3291酸化对细胞周期中的BRCA2-RAD51相互作用的影响.
- 研究了DNA损伤对S3291酸化和RAD51结合的影响.
主要成果:
- 通过循环林依赖性激酶对S3291的酸化在线分裂过程中增加,在S阶段减少.
- S3291酸化抑制了BRCA2与RAD51.1.的相互作用.
- DNA损伤减少了S3291酸化,促进了BRCA2-RAD51相互作用.
结论:
- 化S3291作为一个分子开关,控制RAD51重组活性.
- 这种机制为BRCA2相关的辐射敏感性和癌症倾向提供了洞察力.
相关概念视频
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...
Inhibition 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...
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...
Inhibition 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...


