Figure 2. Schematic of TGFβ’s impact on DDR and consequences of inhibition.
Left: TGFβ promotes HR and NHEJ DNA damage repair by regulating BRCA1 and ATM via miR-182 and inhibiting (faded) error-prone alt-EJ, which makes cells resistant to cytotoxic therapy. Right: Cells that are TGFβ-unresponsive or in which TGFβ signaling is inhibited are deficient in HR and NHEJ and resort to alt-EJ, which increases sensitivity to DNA damage and response to genotoxic chemoradiation.