BRAT1 Impairs DNA Damage Repair in Glioblastoma Cell Lines

Glioblastomas (GBMs) are one of the most malignant brain tumors in adults. This is partly due to potential presence so-called glioma stem-like cells (GSCs), which characterized by expression stemness markers and a resistance radio- chemotherapy. Previous work from us showed that after combination treatment GSCs with arsenic trioxide gossypol, protein BRCA1-associated ATM-activator 1 (BRAT1) was downregulated proteins. largely undescribed, but it has been shown regulate DNA damage signaling through interaction ATM, BRCA1, DNA-PKcs initial stages response. An unpublished analysis The Cancer Genome Atlas Human Protein databases an increased BRAT1 GBMs compared healthy tissues negatively correlated patient survival. Due these findings, our goal analyze radio-sensitizing effect on FCS-grown (i.e., differentiated) highly radio-resistant GBM GSCs. Here, using stable knockdowns BRAT1, we show needed for effective repair irradiation γH2AX-foci assay, whereas dispensable cellular proliferation. A cell death Annexin V/propidium iodide staining revealed first hint downregulation sensitizes irradiation. Moreover, immunofluorescent staining, BRCA1 recruitment sites. Future experiments will aim at systematically analyzing downstream effects depletion determine further interactors. Thus, hope gain deeper understanding mechanism radio-resistance GSCs, also order individually effectiveness radiotherapy.