Fig. 8: Schematic diagram depicting the effect of UNC0379, alone or in combination with adavosertib, on glioblastoma. | Cell Death & Disease

Fig. 8: Schematic diagram depicting the effect of UNC0379, alone or in combination with adavosertib, on glioblastoma.

From: Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth

Fig. 8

a UNC0379 treatment, by inhibiting DNA repair, results in DNA damage accumulation in glioblastoma cells. DNA-damaged p53 proficient cells arrest at the G1/S cell cycle checkpoint; DNA-damaged p53 deficient cells arrest at the G2/M checkpoint; however, some cells can adapt to the checkpoints and restart proliferation. Most of the cells are expected to die in subsequent cell cycles because of the high levels of DNA damage but some cells can survive acquiring more malignant characteristics. b Adavosertib abrogates the cell cycle checkpoints, pushing the cells with UNC0379-induced DNA damage into mitosis where they die by mitotic catastrophe, without the chance of adaptation and survival.

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