微核的cGAS监测将基因组不稳定与先天免疫联系在一起
Karen J Mackenzie1, Paula Carroll1, Carol-Anne Martin1
1MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Nature
|July 25, 2017
概括
核外含有DNA的微核激活循环GMP-AMP合成酶 (cGAS). 这一发现揭示了自我DNA暴露如何触发免疫反应,有可能将基因组不稳定性与自身炎症和癌症监测联系起来.
科学领域:
- 细胞生物学
- 免疫学
- 遗传学
背景情况:
- 为了防止自身免疫反应,DNA通常只限于细胞核.
- 循环GMP-AMP合成酶 (cGAS) 是由双链DNA激活的细胞质DNA传感器,涉及自身炎症疾病和DNA损伤反应.
- 细胞DNA进入细胞质的机制尚未完全理解.
研究的目的:
- 研究细胞DNA如何进入细胞质并激活cGAS.
- 探索微核在cGAS激活和炎症反应中的作用.
- 确定微核的形成是否与基因组不稳定性和疾病有关.
主要方法:
- 在小鼠模型和人类癌细胞中的cGAS定位的观察.
- 微核膜分解及其与cGAS积累的关系的分析.
- 使用活细胞激光微解剖和单细胞转录学研究基因表达.
- 研究微核形成和炎症反应的细胞周期依赖性.
主要成果:
- 在基因组不稳定,DNA损伤或癌细胞中自发的微核中定位.
- 微核膜的分解导致快速的cGAS积累和染色体的激活.
- 微核的形成和随后的促炎反应取决于细胞周期.
- 干扰素刺激的基因表达在微核细胞中被诱导.
结论:
- 微核作为免疫刺激性DNA的重要来源,将自身DNA暴露在细胞质中.
- 微核的cGAS识别是细胞内在的免疫监测机制,可以检测致的过程.
- 这一途径将基因组不稳定性,DNA损伤和自身炎症与癌症检测的潜在影响联系在一起.
相关概念视频
DNA Damage can Stall the Cell Cycle
10.2K
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...
10.2K
Mutagenicity and Carcinogenicity
2.0K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
2.0K
Nucleotide Excision Repair
5.4K
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...
5.4K
Mismatch Repair
6.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.8K
Cancer Prevention
8.2K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
8.2K


