Metabolism-dependent secondary effect of anti-MAPK cancer therapy on DNA repair
Fabien Aubé,
Nicolas Fontrodona,
Laura Guiguettaz
et al.
Abstract:Amino acid bioavailability impacts mRNA translation in a codon-dependent manner. Here, we report that the anti-cancer MAPK inhibitors (MAPKi) decrease the intracellular concentration of aspartate and glutamate in melanoma cells. This coincides with the accumulation of ribosomes on codons corresponding to these amino acids and triggers the translation-dependent degradation of mRNAs encoding aspartate- and glutamate-rich proteins, involved in DNA metabolism such as DNA replication and repair. Consequently, cells… Show more
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