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Wolf-Dietrich HEYER, UC Davis College of Biological Sciences
| When |
Feb 21, 2023
from 02:00 to 03:00 |
|---|---|
| Contact Name | Equipe Piazza, Salle des Thèses |
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BRCA2-mutant cells are defective in homologous recombination, making them vulnerable to the inactivation of other pathways for repairing 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 S phase in BRCA2-deficient cells only after the onset of the following 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, providing a mechanism of why the combined loss is synthetically lethal. We propose that the delay of TMEJ until mitosis ensures the conversion of originally one-ended into two-ended DSBs. Mitotic chromatin condensation might further serve to juxtapose correct break ends and limit chromosomal fusions.
Contact : Aurèle Piazza