Publication: Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress
Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress
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Larsen, B. D., Benada, J., Yung, P. Y. K., Bell, R. A. V., Pappas, G., Urban, V., Ahlskog, J. K., Kuo, T. T., Janscak, P., Megeney, L. A., Elsässer, S. J., Bartek, J., & Sørensen, C. S. (2022). Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress. Science, 376(6592), 476–483. https://doi.org/10.1126/science.abi6378
Abstract
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Abstract
Genotoxic therapy such as radiation serves as a frontline cancer treatment, yet acquired resistance that leads to tumor reoccurrence is frequent. We found that cancer cells maintain viability during irradiation by reversibly increasing genome-wide DNA breaks, thereby limiting premature mitotic progression. We identify caspase-activated DNase (CAD) as the nuclease inflicting these de novo DNA lesions at defined loci, which are in proximity to chromatin-modifying CCCTC-binding factor (CTCF) sites. CAD nuclease activity is governed throu
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- Larsen, Brian D
- Benada, Jan
- Yung, Philip Yuk Kwong
- Bell, Ryan A V
- Pappas, George
- Urban, Vaclav
- Ahlskog, Johanna K
- Kuo, Tia T
- Janscak, Pavel
- Megeney, Lynn A
- Elsässer, Simon J
- Bartek, Jiri
- Sørensen, Claus S
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Larsen, B. D., Benada, J., Yung, P. Y. K., Bell, R. A. V., Pappas, G., Urban, V., Ahlskog, J. K., Kuo, T. T., Janscak, P., Megeney, L. A., Elsässer, S. J., Bartek, J., & Sørensen, C. S. (2022). Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress. Science, 376(6592), 476–483. https://doi.org/10.1126/science.abi6378
