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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 10مصطلحات 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
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::764ce5edab2ceae4c9fc00ac0b4a371cTest
https://doi.org/10.1038/s41556-021-00764-0Test -
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المؤلفون: Sarita Bhetawal, Andrés Cruz-García, Marta Llorens-Agost, Richard D. Wood, Markus Löbrich, Anugrah Gawai, Wolf Dietrich Heyer, Michael Ensminger, Jie Liu, Hang Phuong Le
المصدر: Nature Cell Biology. 24:124-124
مصطلحات موضوعية: Text mining, business.industry, RAD52, Cell Biology, Biology, business, Mitosis, Cell biology
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::9e9a0804f236a8c2b131b736b0b95be4Test
https://doi.org/10.1038/s41556-021-00797-5Test