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About event
The seminar will be onsite and also live-streamed on this link.
This is part of the Principal Investigator Seminar Series.
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Abstract
During gametogenesis, induction of DNA double-strand breaks deliberately occurs in order to allow homologous recombination and crossover formation, essential for faithful segregation of the parental chromosomes into the gametes. The majority of DSBs is shunted into homology-dependent, non-CO-mediated repair, thus restoring genome integrity. Using a proteomic approach, we have identified in Caenorhabditis elegans the BRCA1-BARD1 complex as a putative interactor of PARG-1/PARG, recently shown to be important for homology-mediated repair.
During my talk, I will show that PARG-1 and BRC-1/BRD-1 form indeed a complex in vivo and that contemporary depletion of BRC-1 (or BRD-1) and PARG-1 causes synthetic lethality due to reduced CO formation and aberrant DSB repair. We found that PARG-1 and the BRC-1/BRD-1 complex largely co-localize during meiotic prophase I but their loading is not interdependent, consistent with these factors operating in different pathways. Removal of RPA-1 is impaired in the brc-1; parg-1 double mutants, indicating persistence of single-stranded DNA and unrepaired breaks. Abrogation of KU- or theta-mediated non- homologous end joining uncovers different requirements of these repair pathways in brc-1; parg-1 double mutants, suggesting a complex and multi-layered regulation operated by BRC-1 and PARG-1 in DNA repair pathway choice.
