The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.
The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.
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DOI：
10.1038/ncb3007
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发表时间：
2014-08
影响因子：
21.3
通讯作者：
Stucki M
中科院分区：
文献类型：
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作者：
Larsen DH;Hari F;Clapperton JA;Gwerder M;Gutsche K;Altmeyer M;Jungmichel S;Toledo LI;Fink D;Rask MB;Grøfte M;Lukas C;Nielsen ML;Smerdon SJ;Lukas J;Stucki M
染色体断裂导致核糖体RNA合成的短暂沉默，但涉及的机制仍不清楚。在这里，我们发现了一个反式信号机制，触发泛核沉默的rRNA转录响应DNA损伤。这与瞬时募集的奈梅亨断裂综合征蛋白1（NBS1），DNA损伤反应的中央调节器，进入核仁。我们进一步鉴定了TCOF1-Treacle，一种与核糖体生物发生有关的核仁因子，在Treacher柯林斯综合征中突变，作为NBS1的相互作用伴侣，并证明NBS1在核仁中的转运和积累是Treacle依赖的。最后，我们提供的证据表明，糖浆介导的NBS1招募到核仁调节rRNA沉默在反式存在的远端染色体断裂。
Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in-trans signaling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identified TCOF1-Treacle, a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle-dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in-trans in the presence of distant chromosome breaks.