論文 - 詳細
| RRC ID | 45648 |
|---|---|
| 著者 | Taylor MRG, Špírek M, Chaurasiya KR, Ward JD, Carzaniga R, Yu X, Egelman EH, Collinson LM, Rueda D, Krejci L, Boulton SJ. |
| タイトル | Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. |
| ジャーナル | Cell |
| Abstract |
Repair of DNA double strand breaks by homologous recombination (HR) is initiated by Rad51 filament nucleation on single-stranded DNA (ssDNA), which catalyzes strand exchange with homologous duplex DNA. BRCA2 and the Rad51 paralogs are tumor suppressors and critical mediators of Rad51. To gain insight into Rad51 paralog function, we investigated a heterodimeric Rad51 paralog complex, RFS-1/RIP-1, and uncovered the molecular basis by which Rad51 paralogs promote HR. Unlike BRCA2, which nucleates RAD-51-ssDNA filaments, RFS-1/RIP-1 binds and remodels pre-synaptic filaments to a stabilized, "open," and flexible conformation, in which the ssDNA is more accessible to nuclease digestion and RAD-51 dissociation rate is reduced. Walker box mutations in RFS-1, which abolish filament remodeling, fail to stimulate RAD-51 strand exchange activity, demonstrating that remodeling is essential for RFS-1/RIP-1 function. We propose that Rad51 paralogs stimulate HR by remodeling the Rad51 filament, priming it for strand exchange with the template duplex. |
| 巻・号 | 162(2) |
| ページ | 271-286 |
| 公開日 | 2015-7-16 |
| DOI | 10.1016/j.cell.2015.06.015 |
| PII | S0092-8674(15)00698-4 |
| PMID | 26186187 |
| PMC | PMC4518479 |
| MeSH | Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / metabolism* DNA, Single-Stranded / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* HEK293 Cells Homologous Recombination* Humans Mutation Nuclear Pore Complex Proteins / metabolism Rad51 Recombinase / metabolism* Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / metabolism |
| IF | 38.637 |
| 引用数 | 62 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 23 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2948 tm2134 |