Secretariat, Alumni Association, IDAC
Date	Monday, 15 May 2023, 16:00～17:00
Room	International Conference Room, Center for Smart-Aging Research,1F (IDAC)
Title	RAD52 and BRCA2 regulate pathway usage in double-stranded DNA break repair
Speaker	Prof. Dr. Wolf-Dietrich Heyer
Affiliation	Distinguished Professor and Chair, Department of Microbiology & Molecular Genetics, Co-leader Molecular Oncology Program UC Davis Comprehensive Cancer Center, University of California, CA 95616-8665, USA
Organizer	Akira Yasui (Department of Molecular Oncology・ext8465)
Abstract	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.