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<p>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 <i>PRKDC</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月17日

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  • Martyna Araszkiewicz,
  • Agnieszka Korgul,
  • Katarzyna Tymińska,
  • Urszula Kaźmierczak,
  • Kinga Dyka,
  • Patrycja Chuchała,
  • Renata Grzela,
  • Patrycja Kamińska,
  • Roman Kuczma,
  • Bohdan Paterczyk,
  • Anna Stankiewicz-Drogoń,
  • Beata Wielgus-Kutrowska,
  • Agata Kustra,
  • Michał Fryc,
  • Piotr Bednarczyk,
  • Kamila Maliszewska-Olejniczak

摘要

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.