TGF beta 1 Protects Cells from gamma-IR by Enhancing the Activity of the NHEJ Repair Pathway
- Authors
- Kim, Mi-Ra; Lee, Jeeyong; An, You Sun; Jin, Yeung Bae; Park, In-Chul; Chung, Eunkyung; Shin, Incheol; Barcellos-Hoff, Mary Helen; Yi, Jae Youn
- Issue Date
- Feb-2015
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- MOLECULAR CANCER RESEARCH, v.13, no.2, pp.319 - 329
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR CANCER RESEARCH
- Volume
- 13
- Number
- 2
- Start Page
- 319
- End Page
- 329
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/143854
- DOI
- 10.1158/1541-7786.MCR-14-0098-T
- ISSN
- 1541-7786
- 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.
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