对BRCA1复合体的DNA损伤的影响
1Institute of Cancer Genetics and Department of Pathology, Columbia University College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, New York 10032, USA.
Nature
|November 2, 2001
概括
与之前的发现相反,BRCA1-CtIP复合体在DNA损伤后保持稳定. 通过ATM激酶对CtIP的酸化不会破坏这种相互作用,影响DNA损伤反应基因转录.
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:
- 瘤抑制剂BRCA1蛋白与CtIP相互作用,这是ATM激酶的基质.
- 以前的研究表明,基因毒性压力通过CtIP酸化破坏了BRCA1-CtIP相互作用.
研究的目的:
- 研究电离辐射和ATM激酶介导酸化对BRCA1-CtIP复合体稳定性的影响.
- 确定BRCA1-CtIP复合体中断是否介导DNA损伤反应基因的转录.
主要方法:
- 在照射细胞中研究了BRCA1-CtIP复合体的稳定性.
- 在体内分析了化CtIP异型与BRCA1的相互作用.
- 绘制了CtIP相对于ATM酸化位点的BRCA1结合域.
主要成果:
- 在暴露于电离辐射的细胞中,BRCA1-CtIP复合体保持稳定.
- 通过ATM激酶对CtIP的酸化并不能阻止其与BRCA1.1的体内相互作用.
- CtIP的BRCA1结合域与ATM酸化场所不同.
结论:
- 破坏BRCA1-CtIP复合体不是在基因毒性压力后诱导DNA损伤反应基因的机制.
- 这些发现挑战了Li等人提出的模型. 关于BRCA1-CtIP复合体解离和基因调节.
相关概念视频
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
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The first step of...
The first step of...
Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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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...
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...


