{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE346nnn/GSE346705/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346705"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Elevated dNTP Pool Levels Impair Homologous Recombination and Enhance Glioblastoma Sensitivity to Irradiation and Temozolomide","description":"Glioblastoma (GBM) standard of care includes surgical resection followed by ionizing radiation (IR) and Temozolomide, which induce DNA double-strand breaks. Homologous recombination (HR), a critical DNA double-strand break repair pathway, is augmented in GBM, contributing to resistance and poor patient outcomes. Here, we demonstrate that increasing dNTP levels impairs HR-mediated double-strand break repair, rendering GBM cells sensitive to IR and Temozolomide. Interestingly, combining an elevated dNTP pool level with IR and/or Temozolomide promotes the recruitment of DNA polymer-ase-α/primase, which is typically involved in Okazaki fragment synthesis during DNA replication, to the DNA double-strand break site, thereby interfering with DNA end resection. Specifically, higher dNTP pool levels disrupted the recruitment of HR-associated proteins such as RPA70 and RAD51, an effect reversed by Aphidicolin, a DNA polymerase-α/primase inhibitor. Impaired HR delayed IR- and/or Te-mozolomide-induced DNA double-strand break repair, leading to growth arrest and apoptosis. Furthermore, higher dNTP pool levels led to downregulation of DNA repli-cation and HR-associated genes, while upregulating several pro-apoptotic genes. In-creased sensitivity to IR and Temozolomide was also observed in engineered IR-resistant GBM cell lines and in naturally recurrent patient-derived GBM cells that emerge post-therapy. These findings emphasize how dNTP pool levels regulate HR and uncover a promising vulnerability that could be exploited to overcome resistance to DNA-damaging treatments in GBM and beyond.","dates":{"publication":"2026/09/30"},"accession":"GSE346705","cross_references":{"GSM":["GSM10038860","GSM10038861","GSM10038850","GSM10038851","GSM10038852","GSM10038853","GSM10038854","GSM10038855","GSM10038856","GSM10038857","GSM10038858","GSM10038859"],"GPL":["24676"],"GSE":["346705"],"taxon":["Homo sapiens"],"PMID":["[42794475]"]}}