| Autor: |
Katharina Neuhäuser, Leonie Küper, Hans Christiansen, Natalia Bogdanova |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Clinical and Translational Radiation Oncology, Vol 15, Iss , Pp 99-107 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2405-6308 |
| DOI: |
10.1016/j.ctro.2019.01.006 |
| Popis: |
Background and purpose: The translationally controlled tumor protein 1 (TPT1/TCTP) has been implicated in the intracellular DNA damage response. We tested the role of TPT1 in breast cancer (BC) predisposition and re-evaluated its function in Ataxia-Telangiectasia mutated (ATM)-mediated damage recognition and DNA repair. Material and methods: The TPT1 coding sequence was scanned for mutations in genomic DNA from 200 breast cancer patients. TPT1 was down-regulated through siRNA in breast epithelial and fibroblast cell cultures. ATM activation after irradiation (IR) was analyzed by western blotting, and γH2A.X foci were monitored by immunocytochemistry. Results: The sequencing study identified a novel, potentially damaging missense mutation in a single patient. Silencing of TPT1 did not significantly affect ATM kinase activity and did not impair the initial formation of γH2A.X foci, while we observed a marginally significant effect on residual γH2A.X foci at 6–48 h after IR. Conclusions: TPT1 does not harbor common mutations as BC susceptibility gene. Consistently, TPT1 protein is not required for the recognition of radiation-induced DNA damage via the ATM-dependent pathway and has only slight impact on timely repair. These results may be important when considering TPT1 as a DNA damage marker. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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