ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition.
ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition.
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DOI：
10.1016/j.celrep.2015.08.085
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发表时间：
2015-10-13
期刊：
影响因子：
8.8
通讯作者：
Greenberg RA
中科院分区：
文献类型：
--
作者：
Harding SM;Boiarsky JA;Greenberg RA
DNA双链断裂(DSB)的解决对于抑制基因组的不稳定性至关重要。DSB修复在转录活跃的基因组区域是一个独特的挑战，它与毛细血管扩张突变(ATM)激酶介导的转录沉默相关。尽管对潜在机制有了新的见解，但DSB沉默如何与DNA修复有关仍未确定。我们观察到rDNA内的沉默依赖于持续的双链断裂。非同源末端连接(NHEJ)是DSB修复的主要方式，使转录得以恢复。在持续DSB存在的情况下，ATM依赖的rDNA沉默导致核仁结构的大规模重组，受损的染色质移动到核仁帽区。这些发现确定了依赖ATM的DNA修复的时间和空间控制，并为DSB信号和正在进行的转录之间的通信如何促进基因组完整性提供了见解。
Resolution of DNA double-strand breaks (DSBs) is essential for the suppression of genome instability. DSB repair in transcriptionally active genomic regions represents a unique challenge that is associated with an Ataxia telangiectasia mutated (ATM) kinase-mediated transcriptional silencing. Despite emerging insights into the underlying mechanisms, how DSB silencing connects to DNA repair remains undefined. We observe that silencing within the rDNA depends on persistent DSBs. Non-homologous end-joining (NHEJ) was the predominant mode of DSB repair allowing transcription to resume. ATM-dependent rDNA silencing in the presence of persistent DSBs led to the large-scale reorganization of nucleolar architecture, with movement of damaged chromatin to nucleolar cap regions. These findings identify ATM-dependent temporal and spatial control of DNA repair and provide insights into how communication between DSB signaling and ongoing transcription promotes genome integrity.