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-Structure paper
| タイトル | Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor. |
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| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 21, Issue 11, Page 962-968, Year 2014 |
| 掲載日 | 2014年10月5日 |
著者 | Taha Shahid / Joanna Soroka / Eric Kong / Laurent Malivert / Michael J McIlwraith / Tillman Pape / Stephen C West / Xiaodong Zhang / ![]() |
| PubMed 要旨 | Mutations in BRCA2 increase susceptibility to breast, ovarian and prostate cancers. The product of human BRCA2, BRCA2 protein, has a key role in the repair of DNA double-strand breaks and interstrand ...Mutations in BRCA2 increase susceptibility to breast, ovarian and prostate cancers. The product of human BRCA2, BRCA2 protein, has a key role in the repair of DNA double-strand breaks and interstrand cross-links by RAD51-mediated homologous recombination. Here, we present a biochemical and structural characterization of full-length (3,418 amino acid) BRCA2, alone and in complex with RAD51. We show that BRCA2 facilitates nucleation of RAD51 filaments at multiple sites on single-stranded DNA. Three-dimensional EM reconstructions revealed that BRCA2 exists as a dimer and that two oppositely oriented sets of RAD51 molecules bind the dimer. Single-stranded DNA binds along the long axis of BRCA2, such that only one set of RAD51 monomers can form a productive complex with DNA and establish filament formation. Our data define the molecular mechanism by which this tumor suppressor facilitates RAD51-mediated homologous-recombinational repair. |
リンク | Nat Struct Mol Biol / PubMed:25282148 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 18.5 - 19.5 Å |
| 構造データ | ![]() EMDB-2779: ![]() EMDB-2780: |
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