对ATM和ATR基质的分析显示,广泛的蛋白质网络对DNA损伤有反应
Shuhei Matsuoka1, Bryan A Ballif, Agata Smogorzewska
1Department of Genetics and Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
概括
这项研究揭示了700多种参与DNA损伤反应 (DDR) 的蛋白质,扩大了我们对细胞修复机制的理解,并确定了对哺乳动物细胞至关重要的新蛋白质网络.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞对DNA损伤的反应对于保持基因组稳定至关重要.
- 像ATM和ATR这样的蛋白激酶是DNA损伤反应 (DDR) 的关键媒介.
- 对于DDR路径的全部生理范围的理解尚不完全.
研究的目的:
- 为了全面识别受酸化调节的蛋白质,以应对DNA损伤.
- 探索这些蛋白质的相互联系,并发现新的DDR网络.
- 扩大哺乳动物细胞中已知的DDR组件的范围.
主要方法:
- 对酸盐的大规模蛋白质组分析.
- 通过ATM和ATR激酶酸化的蛋白质的鉴定.
- 识别蛋白质数据集的功能分析.
主要成果:
- 在700多种蛋白质中确定了900多个受调节的酸化位.
- 已识别的蛋白质列表已因已知的DDR因子而显著丰富.
- 发现了许多相互连接的蛋白质模块和网络,以前与DDR无关.
结论:
- 这一蛋白质组数据集提供了对DNA损伤反应的显著扩展视图.
- 这些发现突出显示,参与DDR的蛋白质网络比以前估计的更广泛.
- 这项研究为研究哺乳动物的DNA损伤反应开辟了新的途径.
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...
Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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...
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...
Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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...


