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Our mechanism studies show that PFI-3 exerts the DNA damage-sensitizing effect by directly blocking SWI/SNF's chromatin binding, which leads to defects in DSB repair and aberrations in damage checkpoints, eventually resulting in increase of cell death primarily via necrosis and senescence. This work therefore demonstrates the activity of PFI-3 to sensitize cancer cells to DNA damage and its mechanism of action via SWI/SNF targeting, providing an experimental rationale for developing PFI-3 as a sensitizing agent in cancer chemotherapy. I
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