| 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
|
| リソース情報 |
| 線虫 |
tm1298 |
