Smad7 enhances ATM activity by facilitating the interaction between ATM and Mre11-Rad50-Nbs1 complex in DNA double-strand break repair
- Authors
- Park, Sujin; Kang, Jin Muk; Kim, Staci Jakyong; Kim, Hyojung; Hong, Suntaek; Lee, Young Jae; Kim, Seong-Jin
- Issue Date
- Feb-2015
- Publisher
- SPRINGER BASEL AG
- Keywords
- Carcinogenesis; DNA damage response (DDR); DNA damage checkpoint; Genotoxic stress; Neocarzinostatin (NCS)
- Citation
- CELLULAR AND MOLECULAR LIFE SCIENCES, v.72, no.3, pp.583 - 596
- Journal Title
- CELLULAR AND MOLECULAR LIFE SCIENCES
- Volume
- 72
- Number
- 3
- Start Page
- 583
- End Page
- 596
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10820
- DOI
- 10.1007/s00018-014-1687-z
- ISSN
- 1420-682X
- Abstract
- Genomic instability is one of the representative causes in genetic disorder, where the proper cellular response to DNA damage is essential in maintaining genomic stability. ATM and the Mre11-Rad50-Nbs1 (MRN) complex play critical roles in the cellular response to DNA damage such as DNA double-strand break (DSB). In this study, we report that Smad7 is indispensible in DNA damage response as a novel component of MRN complex. Smad7 enhances cell survival against DNA damage by accelerating ATM dependent DNA repair signaling. In Smad7-deficient mouse embryonic fibroblast cells, the loss of Smad7 decreases ATM activation and inhibits recruitment of ATM to the sites of DSBs. Smad7 interacts with Nbs1, a member of MRN complex, and enhances the interaction between ATM and Nbs1 upon DNA damage response, leading to phosphorylation of downstream substrates. Ectopic expression of Smad7 in the skin of mice enhances the phosphorylation of ATM upon X-irradiation. We found that effect of Smad7 on enhancing DNA repair is independent of its inhibitory activity of TGF-beta signaling. Taken together, our results highlight a critical function of Smad7 in DSB response and establish the novel mechanism in which Smad7 facilitates the recruitment of ATM to the MRN complex through direct interaction with Nbs1.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의예과 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.