在终止转录的部位内源性DNA损伤
Jingjing Liu1,2, Jullian O Perren3,4, Cody M Rogers5
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Nature
|February 19, 2025
概括
研究人员发现了与转录终止相关的DNA损伤的新来源. 这一发现揭示了基因表达过程中的DNA损伤,
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- 已知DNA损伤是癌症,衰老和神经退行性疾病的驱动因素.
- 现有知识确定了三种与转录相关的机制导致DNA损伤.
- 确切的原因和类型的DNA损伤仍然在很大程度上是未知的.
研究的目的:
- 确定新的DNA损伤中间体和来源.
- 发现第四种与转录相关的DNA损伤机制.
- 调查转录终止在DNA损伤中的作用.
主要方法:
- 在细菌和人类细胞中捕获单链DNA (ssDNA) 结尾的工程蛋白.
- 使用DirectRNA测序和同时5'和3'端RNA测序 (SEnd-seq).
- 使用突变RNA聚合酶 (RNAP) 读取终结器.
主要成果:
- 在终止转录的部位确定了内源性DNA损伤作为新源.
- 在大肠杆菌中观察到频繁的自发3'-ssDNA末端焦点,与DNA复制有关.
- 在类似转录终端的序列附近发现了明显的3'-ssDNA末端热点,与RNA3'-终端一致.
结论:
- 转录终止或暂停可以直接促进DNA损伤.
- 这种新发现的机制有助于基因组的不稳定.
- 这些发现提供了有关疾病和衰老的DNA损伤途径的新见解.
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