Loss of PIMREG impairs double-strand break signaling and repair.

Authors

Maria Vitória de Rizzo Gasparini, Laís do Carmo, Giovanna Gonçalves de Almeida, Mariana Siqueira Lacerda Mamede, Isabela David Cardoso, Lígia Arantes Sardinha, Isabela Spido Dias, Jennifer Ann Black, Vanessa Cristina Arfelli, Yun-Chien Chang, Elza Tiemi Sakamoto Hojo, Stephanie Heinzlmeir, Bernhard Kuster, Philipp A Greif, Leticia Fröhlich Archangelo

Published in

Biochimica et biophysica acta. Molecular basis of disease. Pages 168486. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults. It is an aggressive type of tumor with an average overall survival of 12-15 months post-diagnosis. Standard treatment involves surgical resection, followed by radiotherapy and chemotherapy with temozolomide (TMZ). However, resistance to treatment is frequently observed. PIMREG is a marker of proliferation highly expressed across different tumor types, with particularly elevated levels in GBM. Our previous study revealed that PIMREG silencing sensitizes GBM cells to TMZ treatment and affects ATM activation, a key apical kinase involved in DNA damage signaling. Given the emerging significance of PIMREG in the DNA damage response, we sought to explore PIMREG's role in DNA damage repair and signaling in GBM cells exposed to genotoxic agents. Here we assessed the functionally enriched pathways associated with high PIMREG expression in GBM patient samples, analyzed the interactome of PIMREG upon treatment of GBM cells with TMZ and evaluated the impact of PIMREG loss on DNA damage signaling, DNA break formation and the repair of double-strand breaks. Our findings reveal that PIMREG functions as a direct substrate for ATM/ATR kinases, interacts with key DNA repair proteins upon TMZ treatment and actively facilitates the cellular response to chemotherapy- and radiotherapy-induced DNA damage. Taken together, PIMREG may function in the DNA damage response, particularly in the signaling and repair of double strand breaks via homologous recombination in GBM cells. In all, our data suggested high PIMREG expression may affect resistance of GBM cells to treatment.

PMID:
42810418
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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