Karatayeva, Nargis and Hegedűs, Lili and Bhattacharjee, Arindam and Németh, Eszter and Póti, Ádám and Pongor, Lőrinc and Juhász, Gábor and Szüts, Dávid and Burkovics, Péter (2025) The effect of prolonged G-quadruplex stabilization on the functions of human cells. SCIENTIFIC REPORTS, 15 (1). No. 19699. ISSN 2045-2322
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Abstract
Guanine-rich DNA sequences have a propensity to form G-quadruplex structures. These structures play several important biological roles and are potential targets for anticancer drugs. However, no G-quadruplex-stabilizing agent has yet been approved for clinical use. Given that G-quadruplex stabilization is quite promising as a mechanism for novel anticancer therapies, it is crucial to elucidate its effects on healthy human cells. In our study, we modeled a potential human treatment using G4 -stabilizing agents and analyzed their effects on genome integrity, transcriptomic changes, and mitochondrial function focusing on non-cancerous cells to predict potential side effects of such treatments. We found that G-quadruplex stabilization does not compromise genome integrity. However, it can induce persistent alterations in the transcriptomic profile of human cells, including genes encoded on the mitochondrial genome. Notably, certain G-quadruplex-stabilizing agents triggered mitophagy in both human cells and Drosophila melanogaster. In summary, our findings indicate that while G-quadruplex stabilization does not cause genome instability, it may pose potential risks due to its long-term effects on transcription and its ability to induce mitophagy. Therefore, we recommend that all potential drug candidates be thoroughly evaluated for their ability to induce mitophagy and to promote cancer formation in animal models prior to clinical trials. © The Author(s) 2025.
| Item Type: | Article |
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| Additional Information: | Institute of Genetics, HUN-REN, Biological Research Centre, Szeged, Hungary Developmental Biology Group, Agharkar Research Institute, Pune, India Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary Cancer Genomics and Epigenetics Core Group, Hungarian Centre of Excellence for Molecular Medicine, Szeged, Hungary Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Export Date: 16 June 2025; Cited By: 0; Correspondence Address: P. Burkovics; Institute of Genetics, HUN-REN, Biological Research Centre, Szeged, Hungary; email: burkovics.peter@brc.hu |
| Uncontrolled Keywords: | Genome stability; mitophagy; G-quadruplex; PhenDC3; |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 11 Mar 2026 11:50 |
| Last Modified: | 11 Mar 2026 11:50 |
| URI: | https://real.mtak.hu/id/eprint/235550 |
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