DNA repair mechanisms required for meiotic progression involving SWS1-SWSAP1 and BRCA2

During meiotic recombination, homology search and DNA-strand invasion ensure faithful homolog pairing and segregation, to avoid the formation of aneuploidy gametes. These central meiotic steps are catalyzed by two highly conserved recombinases, RAD51 and DMC1, which are assisted by mediator proteins such as BRCA2. RAD51 paralogs are another class of mediator proteins that have been implicated in homologous recombination, but their role in meiosis is poorly understood.
I will present our novel findings uncovering a critical role for the recently identified RAD51 paralog complex, SWS1-SWSAP1, in the early steps of mouse meiotic recombination. In addition, I will show data supporting that this complex has overlapping functions with BRCA2, regulating meiotic RAD51/DMC1 recombination intermediates. Finally, I will present evidence of a switch to a mitotic-like recombination pathway at late meiotic stages that ensures the timely repair of double-stranded breaks before homologs segregate.

Carla did her PhD work in Prof. Noel Lowndes lab at the National University of Ireland Galway. Her dissertation focused on the interplay between cell cycle regulation by the cyclin-dependent kinases and the activation of the DNA damage signaling pathway. Carla then joined the lab of Professor Maria Jasin at the Memorial Sloan Kettering Cancer Center in USA. As a postdoctoral fellow, she investigated the homologous recombination proteins that regulate the activity of the repair recombinases RAD51 and DMC1, focusing on the functions of BRCA2, RAD51 paralogs and RAD54. Carla is now transitioning to the IBMC/i3S in Portugal where she will start her own line of research.