POLθ-mediated end joining is restricted by RAD52 and BRCA2 until the onset of mitosis
| العنوان: | POLθ-mediated end joining is restricted by RAD52 and BRCA2 until the onset of mitosis |
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| المؤلفون: | Markus Löbrich, Wolf Dietrich Heyer, Sarita Bhetawal, Jie Liu, Andrés Cruz-García, Hang Phuong Le, Marta Llorens-Agost, Richard D. Wood, Anugrah Gawai, Michael Ensminger |
| المصدر: | Nat Cell Biol Nature cell biology, vol 23, iss 10 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | DNA End-Joining Repair, DNA polymerase, 1.1 Normal biological development and functioning, genetic processes, RAD52, Mitosis, DNA-Directed DNA Polymerase, Medical and Health Sciences, Article, Double-Stranded, chemistry.chemical_compound, Prophase, Underpinning research, Genetics, Humans, DNA Breaks, Double-Stranded, Homologous Recombination, BRCA2 Protein, biology, DNA Breaks, Cell Cycle, fungi, Cell Biology, Biological Sciences, Rad52 DNA Repair and Recombination Protein, Cell biology, enzymes and coenzymes (carbohydrates), chemistry, Hela Cells, biology.protein, Generic health relevance, Homologous recombination, Function (biology), DNA, Developmental Biology, HeLa Cells |
| الوصف: | BRCA2-mutant cells are defective in homologous recombination, making them vulnerable to the inactivation of other pathways for the repair of DNA double-strand breaks (DSBs). This concept can be clinically exploited but is currently limited due to insufficient knowledge about how DSBs are repaired in the absence of BRCA2. We show that DNA polymerase θ (POLθ)-mediated end joining (TMEJ) repairs DSBs arising during the S phase in BRCA2-deficient cells only after the onset of the ensuing mitosis. This process is regulated by RAD52, whose loss causes the premature usage of TMEJ and the formation of chromosomal fusions. Purified RAD52 and BRCA2 proteins both block the DNA polymerase function of POLθ, suggesting a mechanism explaining their synthetic lethal relationships. We propose that the delay of TMEJ until mitosis ensures the conversion of originally one-ended DSBs into two-ended DSBs. Mitotic chromatin condensation might further serve to juxtapose correct break ends and limit chromosomal fusions. |
| وصف الملف: | application/pdf |
| تدمد: | 1476-4679 1465-7392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::764ce5edab2ceae4c9fc00ac0b4a371cTest https://doi.org/10.1038/s41556-021-00764-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....764ce5edab2ceae4c9fc00ac0b4a371c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764679 14657392 |
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