1miu
From Proteopedia
|
Structure of a BRCA2-DSS1 complex
Contents |
Overview
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.
Disease
Known disease associated with this structure: Split hand/foot malformation, type 1 OMIM:[183600]
About this Structure
1MIU is a Protein complex structure of sequences from Homo sapiens and Mus musculus with HG as ligand. Full crystallographic information is available from OCA.
Reference
BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure., Yang H, Jeffrey PD, Miller J, Kinnucan E, Sun Y, Thoma NH, Zheng N, Chen PL, Lee WH, Pavletich NP, Science. 2002 Sep 13;297(5588):1837-48. PMID:12228710
Page seeded by OCA on Mon Nov 12 18:11:54 2007
