Nucleolar responses to DNA double-strand breaks.
Nucleolar responses to DNA double-strand breaks.
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DOI：
10.1093/nar/gkv1312
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发表时间：
2016-01-29
影响因子：
14.9
通讯作者：
Stucki M
中科院分区：
文献类型：
--
作者：
Larsen DH;Stucki M
维持细胞内稳态是预防转化和疾病的关键。细胞对DNA双链断裂的反应主要由ATM/ATR激酶协调，是维持基因组稳定性和稳态的许多机制之一。在检测到双链断裂（DSB）时，几个信号级联被激活以停止细胞周期进程并启动修复。此外，DNA损伤反应（DDR）控制细胞过程，如转录，剪接和代谢。最近的研究揭示了DDR如何在核仁内运作的方面。看来DDR控制核仁中的转录，不仅当rDNA重复序列中发生DNA断裂时，而且当核DDR被激活时。此外，我们已经获得了第一次深入了解DSB的修复是如何组织在核仁中。总的来说，这些最近的研究提供了DDR如何调节基本细胞功能以维持细胞稳态的更全面的图片。在这篇综述中，我们将总结最近的研究结果，并讨论它们对我们理解DDR如何调节核仁中的转录和修复的影响。
Maintenance of cellular homeostasis is key to prevent transformation and disease. The cellular response to DNA double-strand breaks, primarily orchestrated by the ATM/ATR kinases is one of many mechanisms that serve to uphold genome stability and homeostasis. Upon detection of double-strand breaks (DSBs), several signaling cascades are activated to halt cell cycle progression and initiate repair. Furthermore, the DNA damage response (DDR) controls cellular processes such as transcription, splicing and metabolism. Recent studies have uncovered aspects of how the DDR operates within nucleoli. It appears that the DDR controls transcription in the nucleoli, not only when DNA breaks occur in the rDNA repeats, but also when a nuclear DDR is activated. In addition, we have gained first insights into how repair of DSBs is organized in the nucleolus. Collectively, these recent studies provide a more comprehensive picture of how the DDR regulates basic cellular functions to maintain cellular homeostasis. In this review we will summarize recent findings and discuss their implications for our understanding of how the DDR regulates transcription and repair in the nucleolus.