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

Title
TGF beta 1 Protects Cells from gamma-IR by Enhancing the Activity of the NHEJ Repair Pathway
Authors
신인철
Keywords
DOUBLE-STRAND BREAKS; TGF-BETA; DNA-REPAIR; MESENCHYMAL TRANSITION; GENOMIC INSTABILITY; IONIZING-RADIATION; EPITHELIAL-CELLS; CYCLE ARREST; KINASE; P53
Issue Date
2015-02
Publisher
AMER ASSOC CANCER RESEARCH
Citation
MOLECULAR CANCER RESEARCH, v. 13, NO 2, Page. 319-329
Abstract
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.
URI
http://mcr.aacrjournals.org/content/13/2/319.abstract?http://hdl.handle.net/20.500.11754/22324
ISSN
1557-3125; 1541-7786
DOI
http://dx.doi.org/10.1158/1541-7786.MCR-14-0098-T
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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