Academic Journal
WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer
| العنوان: | WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer |
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| المؤلفون: | Taouis, Karim, Vacher, Sophie, Guirouilh-Barbat, Josée, Camonis, Jacques, Formstecher, Etienne, Popova, Tatiana, Hamy, Anne-Sophie, Petitalot, Ambre, Lidereau, Rosette, Caputo, Sandrine, Zinn-Justin, Sophie, Bièche, Ivan, Driouch, Keltouma, Lallemand, François |
| المساهمون: | Unité de Pharmacogénomique Institut Curie, Institut Curie Paris, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Intégrité du génome et cancers (IGC), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Hybrigenics Services Paris, Residual Tumor & Response to Treatment Laboratory Paris (RT2Lab), Immunité et cancer (U932), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Département Plateforme (PF I2BC), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Oncologique, Université Paris Sciences et Lettres (PSL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0929-1903. |
| بيانات النشر: | CCSD Nature Publishing Group |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience ; The tumor suppressor gene WWOX is localized in an unstable chromosomal region and its expression is decreased or absent in several types of cancer. A low expression of WWOX is associated with a poor prognosis in breast cancer (BC). It has recently been shown that WWOX contributes to genome stability through its role in the DNA damage response (DDR). In breast cancer cells, WWOX inhibits homologous recombination (HR), and thus promotes the repair of DNA double-stranded breaks (DSBs) by non-homologous end joining (NHEJ). The fine-tuning modulation of HR activity is crucial. Its under or overstimulation inducing genome alterations that can induce cancer. MERIT40 is a positive regulator of the DDR. This protein is indispensable for the function of the multi-protein complex BRCA1-A, which suppresses excessive HR activity. MERIT40 also recruits Tankyrase, a positive regulator of HR, to the DSBs to stimulate DNA repair. Here, we identified MERIT40 as a new molecular partner of WWOX. We demonstrated that WWOX inhibited excessive HR activity induced by overexpression of MERIT40. We showed that WWOX impaired the MERIT40-Tankyrase interaction preventing the role of the complex on DSBs. Furthermore, we found that MERIT40 is overexpressed in BC and that this overexpression is associated to a poor prognosis. These results strongly suggest that WWOX, through its interaction with MERIT40, prevents the deleterious impact of excessive HR on BC development by inhibiting MERIT40-Tankyrase association. This inhibitory effect of WWOX would oppose MERIT40-dependent BC development. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41417-023-00626-x |
| الاتاحة: | https://cnrs.hal.science/hal-04260220 https://cnrs.hal.science/hal-04260220v1/document https://cnrs.hal.science/hal-04260220v1/file/s41417-023-00626-x.pdf https://doi.org/10.1038/s41417-023-00626-x |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.508E5C33 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41417-023-00626-x |
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