Fig. 7: Increased tryptophan concentration lead to toxicity and activation of the DNA damage response.

a Tryptophan hypersensitivity upon wars-1 KD. Depletion of WARS-1 leads to the hypersensitivity of worms to the increased concentrations of tryptophan (Trp), shown by reduced percentages of adulthood. At increased concentrations of Trp (>10 mM), worms arrest at the earlier stages of development. (Day 1 is considered the first day of larval development, and worms were observed for nine days. For each condition (wars-1 RNAi and control RNAi) and concentration (0–30 mM), over 20 worms were analyzed. The experiment was repeated at least 3 times. The color gradient bar on the right side indicates the percentages of worms, with green and red showing 100% and 0%, respectively. b Checkpoint activation following acute tryptophan exposure. Exposure to Trp at a higher dosage than physiologic levels for 24 h induced checkpoint activity, as shown by phosphorylation of Checkpoint kinase 1 at serine 345 (CHK-1pSer345). Zooming into the pachytene zone (marked by the dashed squares) indicates the increase in CHK-1 activity upon acute exposure to high levels of Trp (bottom rows). The scale bars represent 20 μm. The experiment was repeated at least three times.