Research Article

BRCA2 Function in DNA Binding and Recombination from a BRCA2-DSS1-ssDNA Structure

Science  13 Sep 2002:
Vol. 297, Issue 5588, pp. 1837-1848
DOI: 10.1126/science.297.5588.1837

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a ∼90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.

  • * To whom correspondence should be addressed. E-mail: nikola{at}xray2.mskcc.org

View Full Text

Related Content