title: Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia.
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.
authors.affiliation: Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, Via Pietro Castellino 111, 80131, Napoli, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Adamo
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Collis
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Adelman
authors.forename: Nicola
authors.initials: N
authors.lastname: Silva
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Horejsi
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Ward
authors.forename: Enrique
authors.initials: E
authors.lastname: Martinez-Perez
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Boulton
authors.forename: Adriana
authors.initials: A
authors.lastname: La Volpe
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D008540:Meiosis / Q000235:genetics; D009154:Mutation / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D003432:Cross-Linking Reagents; D052236:Fanconi Anemia Complementation Group D2 Protein; D051747:DNA-Activated Protein Kinase; D051135:Rad51 Recombinase