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首页> 外文期刊>Journal of Cell Science >Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus
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Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus

机译：核心靶离子照射后局部抑制RRNA转录的RRNA转录的靶向核辐射

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摘要

Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE. Localized ion irradiation with 1-100 carbon ions per point (about 0.3-30 Gy per nucleus) did not lead to overall reduced ribonucleotide incorporation in the targeted nucleolus or other nucleoli of the same cell. However, both 5-ethynyluridine incorporation and Parp1 protein levels were locally decreased at the damaged nucleolar chromatin regions marked by gamma H2AX, suggesting localized inhibition of rRNA transcription. This locally restricted transcriptional inhibition was not accompanied by nucleolar segregation, a structural reorganisation observed after inhibition of rRNA transcription by treatment with actinomycin D or UV irradiation. The presented data indicate that even multiple complex DSBs do not lead to a pan-nucleolar response if they affect only a subnucleolar region.
机译：Nucleoli吸引了对它们作为细胞应激传感器的作用的兴趣以及癌症治疗的潜在目标。 DNA双链断裂（DSB）在核仁rRNA转录和核仁组织中的影响似乎取决于用于引入核仁外的DSB的DSB，DSB频率和存在（或不是）的试剂。为了解决争议，我们将核仁靶向离子微沟蛇的碳离子。局部离子照射，每点1-100个碳离子（每根核约0.3-30Gy）不会导致总体降低的核糖核苷酸掺入同一细胞的其他核仁中。然而，在由γH2AX标记的受损的核核状染色质区域，5-乙炔基脲素掺入和PARP1蛋白水平局部地减少，表明局部抑制RRNA转录。这种局部受限制的转录抑制不伴随核仁偏析，通过用凝集霉素D或UV辐射治疗抑制RRNA转录后观察到的结构重组。呈现的数据表明，如果它们仅影响亚核酸区域，即使多种复合物DSB也不会导致泛核响应。

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