TGF- beta 1 accelerates the DNA damage response in epithelial cells via Smad signaling

• Published in: Biochemical and biophysical research communications Vol. 476; no. 4; pp. 420 - 425
• Main Authors: Lee, Jeeyong, Kim, Mi-Ra, Kim, Hyun-Ji, An, You Sun, Yi, Jae Youn
• Format: Journal Article
• Language: English
• Published: 05.08.2016
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2016.05.136

The evidence suggests that transforming growth factor-beta (TGF- beta ) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF- beta 1 induced DNA ligase IV (Lig4) expression and enhanced the nonhomologous end-joining repair pathway in irradiated cells. In the present study, we investigated the effects of TGF- beta 1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF- beta 1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci ( gamma H2AX). The levels of all three factors were similar right after irradiation regardless of TGF- beta 1 pretreatment. However, they soon thereafter exhibited downregulation in TGF- beta 1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF- beta type I receptor inhibitor (SB431542) or transfections with siRNAs against Smad2/3 or DNA ligase IV (Lig4) reversed this acceleration of the DDR. Furthermore, the frequency of irradiation-induced apoptosis was decreased by TGF- beta 1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF- beta 1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression.