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bioRxiv · 10.1101/2021.06.10.447918

Oxaliplatin kills cells via liquid-liquid demixing of nucleoli

Schmidt, H. B.·Jaafar, Z.·Rodencal, J. J.·Leonetti, M. D.·Dixon, S. J.·Rohatgi, R.·Brandman, O.
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Abstract

Platinum (Pt) compounds such as oxaliplatin are amongst the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here, we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically-relevant concentrations by interfering with the interaction networks that organize nucleoli. This biophysical defect leads to cell cycle arrest, impaired rRNA processing and shutdown of PolI-mediated transcription, ultimately resulting in cell death. We propose that the mechanism of action of oxaliplatin provides a blueprint for the therapeutic targeting of the increasing number of cellular processes being linked to biomolecular condensates.

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Schmidt, H. B., Jaafar, Z., Rodencal, J. J., Leonetti, M. D., Dixon, S. J., Rohatgi, R., Brandman, O.. 2021-06-11. Oxaliplatin kills cells via liquid-liquid demixing of nucleoli. https://doi.org/10.1101/2021.06.10.447918

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