RRC ID 46560
Author Adamo A, Collis SJ, Adelman CA, Silva N, Horejsi Z, Ward JD, Martinez-Perez E, Boulton SJ, La Volpe A.
Title Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia.
Journal 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.
Volume 39(1)
Pages 25-35
Published 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 14.248
Times Cited 141
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
C.elegans tm1298