EMBO Fellows Meeting 2012

Laurent Malivert
EMBO Fellows Meeting 2012
Biochemical and structural analysis of the breast cancer tumour suppressor BRCA2
Abstract
Germline mutations in the BRCA2 gene confer an elevated lifetime risk of developing breast, ovarian, and other
cancers. The tumour suppressor function relates to a role for BRCA2 protein in the homologous recombination
(HR)-mediated DNA repair of DNA double-strand breaks (DSB). BRCA2 contains eight BRC repeats, which
interact with RAD51, a protein that plays a central role in recombinational repair. In this process, the ends cut
as DSB are resected and exposed as single-stranded DNA (ssDNA). BRCA2 is thought to target RAD51 onto the
ssDNA, mediating the assembly of a RAD51-ssDNA nucleoprotein filament. We recently purified the BRCA2
protein (3,418 amino acids) and found that it forms dimers in solution. The protein binds specifically to single
rather than double-stranded DNA consistent with a role in the loading of RAD51 to these sites. We are
currently studying the mechanism of RAD51 loading by BRCA2 by biochemical approaches and are
investigating the three-dimensional structure of BRCA2 by electron microscopy.
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Hertfordshire, UK
14-17 June 2012, Heidelberg, Germany