title: TGFβ1 protects cells from γ-IR by enhancing the activity of the NHEJ repair pathway.
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.
  
  
  CONCLUSIONS
  These findings provide new insight and a possible approach to controlling genotoxic stress by the TGFβ signaling pathway.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul, Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul, Korea.
authors.forename: Jeeyong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul, Korea.
authors.forename: You Sun
authors.initials: YS
authors.lastname: An
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, National Primate Research Center, Cheongju-si, Chungbuk, Korea.
authors.forename: Yeung Bae
authors.initials: YB
authors.lastname: Jin
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiation and Medical Sciences, Seoul, Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering, College of Life Science, Kyung Hee University, Yongin, Gyeonggi-do, Korea.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Chung
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology and Cell Biology, New York University of Medicine, New York, New York.
authors.forename: Mary Helen
authors.initials: MH
authors.lastname: Barcellos-Hoff
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiation and Medical Sciences, Seoul, Korea. yjy_71@kcch.re.kr.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Yi
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000187:drug effects* / Q000528:radiation effects; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; C000607893:LIG4 protein, human; D051785:Smad Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D011088:DNA Ligases; D000072481:DNA Ligase ATP