在没有DNA病变的情况下,细胞DNA损伤反应的激活
1National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. soutogle@mail.nih.gov
概括
稳定地将DNA修复因子与染色质结合,可以在没有实际DNA损伤的情况下触发DNA损伤反应 (DDR). 这个过程涉及ATM和DNA-PK,突出显示染色体协会是关键的DDR激活步骤.
科学领域:
- 细胞生物学 细胞生物学
- 分子遗传学 分子遗传学
- 生物化学 生物化学
背景情况:
- DNA损伤反应 (DDR) 对于保持基因组稳定性至关重要.
- 通过DNA修复复合体感知DNA损伤并激活DDR的精确机制尚未完全理解.
研究的目的:
- 为了调查DDR激活是否严格要求DNA损伤.
- 阐明DNA修复因子与染色质结合在DDR启动中的作用.
主要方法:
- 在没有DNA损伤的情况下,将DNA修复因子向染色质.
- 通过ATM和DNA-PK依赖途径评估DDR激活.
- 在修复复合体内分析蛋白质-蛋白质相互作用.
主要成果:
- 长时间将DNA修复因子与染色质结合,可以独立于DNA损伤诱导DDR.
- ATM (ataxia telangiectasia突变) 和DNA-PK (DNA依赖蛋白激酶) 对于这种独立于损伤的DDR是必不可少的.
- 在修复复合体内观察到蛋白质相互作用的等级,这表明信号放大.
结论:
- 激活DDR并不一定会损害DNA.
- 稳定的DNA修复因子与染色质的关联是DDR启动,放大和维护的关键触发因素.
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...
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...
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...
Translesion DNA Polymerases
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
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...


