| Autor: |
Xinzhu Deng, David Michaelson, Jason Tchieu, Jin Cheng, Diana Rothenstein, Regina Feldman, Sang-gyu Lee, John Fuller, Adriana Haimovitz-Friedman, Lorenz Studer, Simon Powell, Zvi Fuks, E Jane Albert Hubbard, Richard Kolesnick |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 10, Iss 6, p e0127862 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0127862 |
| Popis: |
Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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