Title:
Promotion of BRCA2-dependent Homologous Recombination by DSS1
Speaker: Dr. Patrick Sung, Yale University
BRCA2 plays a key role in chromosome damage repair via homologous recombination. Importantly,
mutations in BRCA2 are linked to familial breast and other cancers, and also to Fanconi anemia. A critical
step in HR is the pairing of homologous DNA molecules that is catalyzed by a filamentous form of the
RAD51 recombinase bound to ssDNA. The assembly of this nucleoprotein filament is rate limiting owing
to the slow nucleation of RAD51 onto ssDNA and DNA binding competition by replication protein A
(RPA). The inhibitory effect of RPA can be lessened by BRCA2 in vitro. However, BRCA2 does not interact
with RPA and how it mediates the handoff of ssDNA from RPA to RAD51 is unknown. We have found
that RPA-RAD51 exchange on ssDNA is strongly dependent on DSS1 and have provided evidence that
DSS1 acts via RPA binding and DNA mimicry.