http://www.cnr.it/ontology/cnr/individuo/prodotto/ID26954
Preventing Nonhomologous End Joining Suppresses DNA Repair Defects of Fanconi Anemia (Articolo in rivista)
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- Label
- Preventing Nonhomologous End Joining Suppresses DNA Repair Defects of Fanconi Anemia (Articolo in rivista) (literal)
- Anno
- 2010-01-01T00:00:00+01:00 (literal)
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- Adele Adamo; Spencer J. Collis; Carrie A. Adelman; Nicola Silva; Zuzana Horejsi; Jordan D. Ward; Enrique Martinez-Perez; Simon J. Boulton; Adriana La Volpe (literal)
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- C. elegans FCD-2 prevents illegitimate repair of DSBs in meiotic and mitotic cells
Eliminating NHEJ by lig-4 deletion rescues the ICL repair defects of fcd-2 mutants
Loss of NHEJ suppresses the ICL sensitivity of FA mammalian cells
FANCD2 prevents improper engagement of DNA-PKcs with sites of replication stress (literal)
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- ISI Web of Science (WOS) (literal)
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- Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, Via Pietro Castellino 111, 80131, Napoli, Italy
DNA Damage Response Laboratory, London Research Institute, Clare Hall, South Mimms, EN6 3LD, UK
Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK
Department of Structural and Functional Biology, University of Naples, Federico II, Complesso di Monte S. Angelo, 80138, Napoli, Italy
Clinical Sciences Division, Imperial College, Du Cane Road, London, W12 0NN, UK (literal)
- Titolo
- Preventing Nonhomologous End Joining Suppresses DNA Repair Defects of Fanconi Anemia (literal)
- 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 (literal)
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