TGF beta 1 Protects Cells from gamma-IR by Enhancing the Activity of the NHEJ Repair Pathway

Several groups have reported that TGF beta 1 regulates cellular responses to gamma-irradiation; however, the exact mechanism has not been fully elucidated. In the current study, the role of TGF beta 1 in cellular responses to gamma-irradiation was investigated in detail. The data indicate that TGF beta 1 pretreatment decreased the aftermath of ionizing radiation (IR)-induced DNA damage in a SMAD-dependent manner. To determine the underlying mechanism for these effects, the extent of IR-induced DNA repair activity in the presence or absence of TGF beta 1 was examined. Studies reveal that TGF beta 1 upregulated DNA ligase IV (Lig4), augmented IR-induced nuclear retention of the DNA ligase, and enhanced nonhomologous end-joining (NHEJ) repair activity. In addition, knockdown of Lig4 reduced the TGF beta 1-induced protection against IR. Overall, these data indicate that TGF beta 1 facilitates the NHEJ repair process upon gamma-irradiation and thereby enhances long-term survival. (C) 2014 AACR.