論文 - 詳細
| RRC ID | 46560 |
|---|---|
| 著者 | Adamo A, Collis SJ, Adelman CA, Silva N, Horejsi Z, Ward JD, Martinez-Perez E, Boulton SJ, La Volpe A. |
| タイトル | Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. |
| ジャーナル | Mol Cell |
| Abstract |
Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with DNA repair defects and infertility, yet the precise function of the FA proteins in genome maintenance remains unclear. Here we report that C. elegans FANCD2 (fcd-2) is dispensable for normal meiotic recombination but is required in crossover defective mutants to prevent illegitimate repair of meiotic breaks by nonhomologous end joining (NHEJ). In mitotic cells, we show that DNA repair defects of C. elegans fcd-2 mutants and FA-deficient human cells are significantly suppressed by eliminating NHEJ. Moreover, NHEJ factors are inappropriately recruited to sites of replication stress in the absence of FANCD2. Our findings are consistent with the interpretation that FA results from the promiscuous action of NHEJ during DNA repair. We propose that a critical function of the FA pathway is to channel lesions into accurate, as opposed to error-prone, repair pathways. |
| 巻・号 | 39(1) |
| ページ | 25-35 |
| 公開日 | 2010-7-9 |
| DOI | 10.1016/j.molcel.2010.06.026 |
| PII | S1097-2765(10)00493-4 |
| PMID | 20598602 |
| MeSH | Animals Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism Cross-Linking Reagents / metabolism Crossing Over, Genetic DNA Breaks, Double-Stranded DNA Repair / genetics* DNA Replication DNA-Activated Protein Kinase / metabolism Fanconi Anemia / genetics* Fanconi Anemia / pathology Fanconi Anemia Complementation Group D2 Protein / deficiency Fanconi Anemia Complementation Group D2 Protein / metabolism Humans Meiosis / genetics Mutation / genetics Rad51 Recombinase / metabolism Recombination, Genetic* Stress, Physiological |
| IF | 15.584 |
| 引用数 | 191 |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 10 |
| 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 | tm1298 |