Academic Journal
Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges
| Title: | Modulation of OGG1 enzymatic activities by small molecules, promising tools and current challenges |
|---|---|
| Authors: | Renaudin, Xavier, Campalans, Anna |
| Contributors: | Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Campalans lab has received financial support from the Agence Nationale de la recherche (ANR-OXIREPTRA and ANR-TIROX), La Ligue contre le Cancer, the graduate school Life sciences and Health (GS-LSH) from the Université Paris-Saclay, Electricité de France and the CEA., ANR-23-CE12-0025,OxiREPTRA,Les dommages oxydatifs de l'ADN et OGG1 à l'interface entre réparation de l'ADN et régulation de la transcription(2023), ANR-24-CE12-2431,Tirox,Blessures transcriptionnelles et rétablissement en réponse au stress oxidatif(2024) |
| Source: | ISSN: 1568-7864. |
| Publisher Information: | CCSD Elsevier |
| Publication Year: | 2025 |
| Collection: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: | Transcriptional regulation, Small molecules, Oxidative DNA damage, OGG1 modulators, Inflammation, Cancer, Base excision repair, MESH: Animals, DNA Damage, DNA Glycosylases* / antagonists & inhibitors, DNA Glycosylases* / metabolism, DNA Repair* / drug effects, Enzyme Inhibitors* / pharmacology, Humans, Neoplasms / drug therapy, Neoplasms / genetics, Oxidative Stress, Small Molecule Libraries* / pharmacology, [SDV]Life Sciences [q-bio] |
| Description: | International audience ; Oxidative DNA damage, resulting from endogenous cellular processes and external sources plays a significant role in mutagenesis, cancer progression, and the pathogenesis of neurological disorders. Base Excision Repair (BER) is involved in the repair of base modifications such as oxidations or alkylations as well as single strand breaks. The DNA glycosylase OGG1, initiates the BER pathway by the recognition and excision of 8oxoG, the most common oxidative DNA lesion, in both nuclear and mitochondrial DNA. Beyond DNA repair, OGG1 modulates transcription, particularly pro-inflammatory genes, linking oxidative DNA damage to broader biological processes like inflammation and aging. In cancer therapy, BER inhibition has emerged as a promising strategy to enhance treatment efficacy. Targeting OGG1 sensitizes cells to chemotherapies, radiotherapies, and PARP inhibitors, presenting opportunities to overcome therapy resistance. Additionally, OGG1 activators hold potential in mitigating oxidative damage associated with aging and neurological disorders. This review presents the development of several inhibitors and activators of OGG1 and how they have contributed to advance our knowledge in the fundamental functions of OGG1. We also discuss the new opportunities they provide for clinical applications in treating cancer, inflammation and neurological disorders. Finally, we also highlight the challenges in targeting OGG1, particularly regarding the off-target effects recently reported for some inhibitors and how we can overcome these limitations. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISBN: | 978-1-56878-642-1 1-56878-642-5 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/40120404; PUBMED: 40120404 |
| DOI: | 10.1016/j.dnarep.2025.103827 |
| Availability: | https://u-paris.hal.science/hal-05110034 https://u-paris.hal.science/hal-05110034v1/document https://u-paris.hal.science/hal-05110034v1/file/1-s2.0-S1568786425000230-main.pdf https://doi.org/10.1016/j.dnarep.2025.103827 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: | edsbas.18B01931 |
| Database: | BASE |
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