取决于ATM的染色体变化沉默转录在cis到DNA的双链断裂
Niraj M Shanbhag1, Ilona U Rafalska-Metcalf, Carlo Balane-Bolivar
1Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Cell
|June 17, 2010
概括
DNA双链断裂触发了一个ATM激酶依赖的转录沉默程序. 这一过程涉及基因组无处不在,并影响DNA断裂附近的染色质结构.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- DNA双链断裂 (DSBs) 诱导显著的染色质变化.
- ATM激酶在细胞对DSB的反应中起着关键作用.
- 基因组H2A无处不在 (uH2A) 与DSB修复和转录抑制有关.
研究的目的:
- 为了研究 uH2A介导的转录抑制在DSBs的背景下被保存的假设.
- 描述DSB的ATM依赖的转录性沉默程序.
- 确定参与DSB诱导沉默及其逆转的分子参与者.
主要方法:
- 利用了一种新型的记者系统来对修复蛋白质招募和局部转录的单细胞可视化.
- 采用基因方法来评估ATM,RNF8,RNF168和USP16在DSB附近的转录调节中的作用.
主要成果:
- 描述了在cis到DSB中发生的ATM依赖的转录沉默程序.
- 证明ATM阻止RNA聚合酶II延长依赖的染色质脱凝,远离DSBs.
- 显示静音对RNF8和RNF168的部分依赖,并依赖USP16进行静音逆转.
结论:
- ATM 激酶调节一个转录沉默程序,以响应DNA双链断裂.
- 翻译后的修改,包括H2A,介于DNA修复和转录调节之间的交叉声调.
- 这些发现提供了关于DNA损伤反应期间染色质修饰的复杂相互作用的见解.
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