DSS1 and ssDNA regulate oligomerization of BRCA2.

The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic analysis (3), but the functional significance of the different BRCA2 assemblies remains to be determined. Here, we used biochemistry and electron microscopic imaging to demonstrate that the multimerization of BRCA2 is counteracted by DSS1 and ssDNA. When validating the findings, we identified three self-interacting regions and two types of self-association, the N-to-C terminal and the N-to-N terminal interactions. The N-to-C terminal self-interaction of BRCA2 is sensitive to DSS1 and ssDNA. The N-to-N terminal self-interaction is modulated by ssDNA. Our results define a novel role of DSS1 to regulate BRCA2 in an RPA-independent fashion. Since DSS1 is required for BRCA2 function in recombination, we speculate that the monomeric and oligomeric forms of BRCA2 might be active for different cellular events in recombinational DNA repair and replication fork stabilization.

Patient-Centered Team-Based Learning in Pre-Clinical Curriculum Supporting the Application of Knowledge to Real-World Clinical Experience.

We report an active learning session which effectively supported 1st year medical students applying their learning experience in a clinical setting. A team-based learning (TBL) on familial hypercholesterolemia (FH) with a live patient was given to deliver basic genetics knowledge in a clinically relevant context. Subsequently, two participating students applied their learning experience by presenting a differential diagnosis of homozygous FH in a patient at a medical mission in Central America. We propose that combining active learning with clinically relevant scenarios effectively fosters student's clinical reasoning skills and can bridge the perceived gap between basic science and clinical education.