RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells

King, Harry O. and Brend, Tim and Payne, Helen L. and Wright, Alexander and Ward, Thomas A. and Patel, Karan and Egnuni, Teklu and Stead, Lucy F. and Patel, Anjana and Wurdak, Heiko and Short, Susan C. (2017) RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells. Stem Cell Reports, 8 (1). pp. 125-139. ISSN 2213-6711

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Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation. In GSCs, the small-molecule RAD51 inhibitors RI-1 and B02 prevent RAD51 focus formation, reduce DNA DSB repair, and cause significant radiosensitization. We further demonstrate that treatment with these agents combined with radiation promotes loss of stem cells defined by SOX2 expression. This indicates that RAD51-dependent repair represents an effective and specific target in GSCs.

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Journal Article
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Stem Cell Reports
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Deposited On:
03 Jul 2018 10:00
Last Modified:
20 Sep 2023 01:13