1. Model of SWI/SNF, Keap1, and C9orf82 regulating different phases of Topo II poison-induced DNA break formation and DDR. Topo II poisons like doxorubicin induce DNA DSBs by trapping Topo II on the DNA. If not sufficiently repaired, this leads to cell death.
Model of SWI/SNF, Keap1, and C9orf82 regulating different phases of Topo II poison-induced DNA break formation and DDR. Topo II poisons like doxorubicin induce DNA DSBs by trapping Topo II on the DNA. If not sufficiently repaired, this leads to cell death. Keap1 controls the expression of Topo IIα, while SWI/SNF regulates the loading and hereby activity of Topo IIα. Loss of these genes therefore attenuates DNA DSB formation by Topo II poisons. In the next phase of the DNA breaks and repair cycle, C9orf82 controls DNA repair. Loss of C9orf82 accelerates DNA repair, reducing cell death induced by Topo II poisons.
Ruud H. Wijdeven et al. Cancer Res 2015;75:
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