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Author Lee, Jeeyong ♦ Kim, Mi-Ra ♦ Kim, Hyun-Ji ♦ An, You Sun ♦ Yi, Jae Youn
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ BIOLOGICAL PATHWAYS ♦ BIOLOGICAL REPAIR ♦ DNA ♦ DNA DAMAGES ♦ GROWTH FACTORS ♦ HISTONES ♦ IN VIVO ♦ IRRADIATION ♦ LIGASES ♦ RECEPTORS ♦ SIGNALS
Abstract The evidence suggests that transforming growth factor-beta (TGF-β) regulates the DNA-damage response (DDR) upon irradiation, and we previously reported that TGF-β1 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-β1 on the irradiation-induced DDRs of A431 and HaCaT cells. Cells were pretreated with or without TGF-β1 and irradiated. At 30 min post-irradiation, DDRs were detected by immunoblotting of phospho-ATM, phospho-Chk2, and the presence of histone foci (γH2AX). The levels of all three factors were similar right after irradiation regardless of TGF-β1 pretreatment. However, they soon thereafter exhibited downregulation in TGF-β1-pretreated cells, indicating the acceleration of the DDR. Treatment with a TGF-β 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-β1 pretreatment in vivo, but this effect was abrogated by SB431542. These results collectively suggest that TGF-β1 could enhance cell survival by accelerating the DDR via Smad signaling and Lig4 expression. -- Highlights: •TGF-β1 pretreatment accelerates γ-radiation-induced DNA damage response. •TGF-β1-accelerated DNA damage response is dependent on Smad signaling and DNA Ligase IV. •TGF-β1 pretreatment protects epithelial cells from γ-radiation in vivo.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-08-05
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 476
Issue Number 4


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