TGFβ1 protects cells from γ-IR by enhancing the activity of the NHEJ repair pathway

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Title
TGFβ1 protects cells from γ-IR by enhancing the activity of the NHEJ repair pathway
Author(s)
M R Kim; J Lee; Y S An; Yeung Bae Jin; I C Park; E Chung; I Shin; M H Barcellos-Hoff; J Y Yi
Bibliographic Citation
Molecular Cancer Research, vol. 13, no. 2, pp. 319-329
Publication Year
2015
Abstract
Several groups have reported that TGFβ1 regulates cellular responses to γ-irradiation; however, the exact mechanism has not been fully elucidated. In the current study, the role of TGFβ1 in cellular responses to γ-irradiation was investigated in detail. The data indicate that TGFβ1 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 TGFβ1 was examined. Studies reveal that TGFβ1 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 TGFβ1-induced protection against IR. Overall, these data indicate that TGFβ1 facilitates the NHEJ repair process upon γ-irradiation and thereby enhances long-term survival. Implications: These findings provide new insight and a possible approach to controlling genotoxic stress by the TGFβ signaling pathway.
ISSN
1541-7786
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/1541-7786.MCR-14-0098-T
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
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