Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis

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Potent, Reversible, and Specific Chemical Inhibitors of Eukaryotic Ribosome Biogenesis

All cellular proteins are synthesized by ribosomes, whose biogenesis in eukaryotes is a complex multi-step process completed within minutes. Several chemical inhibitors of ribosome function are available and used as tools or drugs. By contrast, we lack potent validated chemical probes to analyze the dynamics of eukaryotic ribosome assembly. Here, we combine chemical and genetic approaches to di...

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Ribosomes play a pivotal role in the molecular life of every cell. Moreover, synthesis of ribosomes is one of the most energetically demanding of all cellular processes. In eukaryotic cells, ribosome biogenesis requires the coordinated activity of all three RNA polymerases and the orchestrated work of many (>200) transiently associated ribosome assembly factors. The biogenesis of ribosomes is a...

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The effects of many chemotherapeutic drugs on ribosome biogenesis have been underestimated for a long time. Indeed, many drugs currently used for cancer treatment--and which are known to either damage DNA or hinder DNA synthesis--have been shown to exert their toxic action mainly by inhibiting rRNA synthesis or maturation. Moreover, there are new drugs that have been proposed recently for cance...

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ژورنال

عنوان ژورنال: Cell

سال: 2016

ISSN: 0092-8674

DOI: 10.1016/j.cell.2016.08.070