Work

Expression of DNA-damage response genes after exposure to high LET particles used in BNCT in glioblastoma cells with altered radiosensitivity

Year: 2025

Type: article

Abstract: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a central role in the repair of double-strand breaks (DSBs), but its deficiency alters the broader DNA damage response in glioblastoma cells exposed to α particle irradiation. Here, we investigated transcriptional changes in DNA repair pathways and cellular radiosensitivity in two isogenic glioblastoma cell lines differing in DNA-PKcs status: M059J (DNA-PKcs-deficient) and M059K (DNA-PKcs-proficient). Using pathway-focused qPCR, we profiled 30 genes involved in key DNA repair pathways and evaluated cell survival by clonogenic and MTT assays. M059J cells, despite DNA-PKcs deficiency, exhibited comparable survival fractions and higher metabolic activity than DNA-PKcs-proficient M059K cells following α particle irradiation. Irradiated M059J cells exhibited broad transcriptional upregulation of genes involved in double-strand break repair, single-strand break repair, mismatch repair, and nucleotide excision repair, reflecting compensatory activation of multiple repair mechanisms. In contrast, M059K cells displayed a restricted response, characterized primarily by strong PRKDC upregulation, the gene encoding DNA-PKcs. These findings highlight the pivotal role of DNA-PKcs status in shaping the DNA damage response and radiosensitivity of glioblastoma cells. Targeting compensatory repair pathways in DNA-PKcs-deficient tumors may offer novel strategies for radiosensitization in glioblastoma therapy.

Source: Scientific Reports

DOI: 10.1038/s41598-025-32635-1