Academic Journal
The one‐carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation
| العنوان: | The one‐carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation |
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| المؤلفون: | Petra Marttila, Nadilly Bonagas, Christina Chalkiadaki, Hannah Stigsdotter, Korbinian Schelzig, Jianyu Shen, Crystal M. Farhat, Amber Hondema, Julian Albers, Elisée Wiita, Azita Rasti, Ulrika Warpman Berglund, Ana Slipicevic, Oliver Mortusewicz, Thomas Helleday |
| المصدر: | Molecular Oncology, Vol 18, Iss 9, Pp 2179-2195 (2024) |
| بيانات النشر: | Wiley, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | DSB repair, homologous recombination, ionizing radiation, MTHFD2, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | The one‐carbon metabolism enzyme bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is among the most overexpressed proteins across tumors and is widely recognized as a promising anticancer target. While MTHFD2 is mainly described as a mitochondrial protein, a new nuclear function is emerging. Here, we observe that nuclear MTHFD2 protein levels and association with chromatin increase following ionizing radiation (IR) in an ataxia telangiectasia mutated (ATM)‐ and DNA‐dependent protein kinase (DNA‐PK)‐dependent manner. Furthermore, repair of IR‐induced DNA double‐strand breaks (DSBs) is delayed upon MTHFD2 knockdown, suggesting a role for MTHFD2 in DSB repair. In support of this, we observe impaired recruitment of replication protein A (RPA), reduced resection, decreased IR‐induced DNA repair protein RAD51 homolog 1 (RAD51) levels and impaired homologous recombination (HR) activity in MTHFD2‐depleted cells following IR. In conclusion, we identify a key role for MTHFD2 in HR repair and describe an interdependency between MTHFD2 and HR proficiency that could potentially be exploited for cancer therapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13645 |
| URL الوصول: | https://doaj.org/article/d2259d5f9c79453fb3ba60c0c62266eb |
| رقم الانضمام: | edsdoj.2259d5f9c79453fb3ba60c0c62266eb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13645 |