核心spliceosome作为非正规ATM信号的目标和效应器
Maria Tresini1, Daniël O Warmerdam2, Petros Kolovos3
1Department of Genetics, Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.
Nature
|June 25, 2015
概括
对DNA损伤的反应涉及连接体位移和R循环形成,激活ATM激酶. 这种反循环增强了替代拼接,这对于在DNA损伤后维持组织平衡至关重要.
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:
- 组织平衡依赖于DNA损伤反应途径.
- 通过mRNA水平和替代拼接,DNA损伤会影响基因表达.
- 替代拼接在细胞对DNA损伤的反应中起着至关重要的作用.
研究的目的:
- 为了研究结合体在对DNA损伤的反应中的作用.
- 阐明链接DNA病变的机制,spliceosome移位和信号通路.
- 定义R循环形成在DNA损伤反应中的功能.
主要方法:
- 在DNA病变中分析结合体动力学.
- 研究RNA聚合酶暂停和R循环形成.
- 评估ATM激酶激活及其下游影响.
- 对替代拼接变化的全基因组分析.
主要成果:
- 转录阻断的DNA病变会导致晚期结合酶体的染色质位移.
- 确定了一种涉及ATM激酶和结合体组织的积极反循环.
- 由暂停的RNA聚合酶触发的R-循环形成激活了ATM.
- ATM信号进一步阻碍了结合体组织,并增强了紫外线诱导的替代拼接.
结论:
- 通过DNA病变激活R循环依赖的ATM对于非复制细胞中的DNA损伤反应至关重要.
- 在这个过程中,spliceosome的移位是关键事件.
- 这种机制突出了DNA修复,拼接和信号传递之间的新相互作用.
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