Artículo
SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells
Autor/es | Adanma Obara, Elisabeth Anne
Aguilar Morante, Diana ![]() ![]() ![]() ![]() ![]() ![]() ![]() Darling Rasmussen, Rikke Frias, Alex Vitting-Serup, Kristoffer Chieh Lim, Yi Hamerlik, Petra |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2020 |
Fecha de depósito | 2023-11-09 |
Publicado en |
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Resumen | Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin ... Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma. |
Cita | Adanma Obara, E.A., Aguilar Morante, D., Darling Rasmussen, R., Frias, A., Vitting-Serup, K., Chieh Lim, Y. y Hamerlik, P. (2020). SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells. Nature Communications, 11 (1), 1-14. https://doi.org/10.1038/s41467-020-18549-8. |
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