1IYJ

STRUCTURE OF A BRCA2-DSS1 COMPLEX

Summary for 1IYJ

• Entry DOI: 10.2210/pdb1iyj/pdb
• Related: 1MIU 1MJE
• Descriptor: Deleted in split hand/split foot protein 1, breast cancer susceptibility (2 entities in total)
• Functional Keywords: tumor suppressor, breast cancer susceptibility, dna-binding, gene regulation-antitumor protein complex, gene regulation/antitumor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 200018.88

Authors

Pavletich, N.P.,Jeffrey, P.D.,Yang, H.J. (deposition date: 2002-08-28, release date: 2002-10-02, Last modification date: 2023-12-27)

Primary citation

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.
BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure.
Science, 297:1837-1848, 2002

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.

PubMed: 12228710
DOI: 10.1126/science.297.5588.1837

Experimental method

X-RAY DIFFRACTION (3.4 Å)