Download MendeleyBRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure
Yang, H., Jeffrey, P.D., Miller, J., Kinnucan, E., Sun, Y., Thoma, N.H., Zheng, N., Chen, P.L., Lee, W.H., Pavletich, N.P.(2002) Science 297: 1837-1848
- PubMed: 12228710
- DOI: https://doi.org/10.1126/science.297.5588.1837
- Primary Citation of Related Structures:
1IYJ, 1MIU, 1MJE - PubMed 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 approximately 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.
Organizational Affiliation:
Department of Pharmacology, Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.
