title: Growth defect and mutator phenotypes of RecQ-deficient Neurospora crassa mutants separately result from homologous recombination and nonhomologous end joining during repair of DNA double-strand breaks.
abstract: RecQ helicases function in the maintenance of genome stability in many organisms. The filamentous fungus Neurospora crassa has two RecQ homologs, QDE3 and RECQ2. We found that the qde-3 recQ2 double mutant showed a severe growth defect. The growth defect was alleviated by mutation in mei-3, the homolog of yeast RAD51, which is required for homologous recombination (HR), suggesting that HR is responsible for this phenotype. We also found that the qde-3 recQ2 double mutant showed a mutator phenotype, yielding mostly deletions. This phenotype was completely suppressed by mutation of mus-52, a homolog of the human KU80 gene that is required for nonhomologous end joining (NHEJ), but was unaffected by mutation of mei-3. The high spontaneous mutation frequency in the double mutant is thus likely to be due to NHEJ acting on an elevated frequency of double-strand breaks (DSBs) and we therefore suggest that QDE3 and RECQ2 maintain chromosome stability by suppressing the formation of spontaneous DSBs.
authors.affiliation: Laboratory of Genetics, Department of Regulation Biology, Faculty of Science, Saitama University, 338-8570 Saitama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics*; D034961:Antigens, Nuclear / Q000235:genetics; D019457:Chromosome Breakage; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D000072200:Ku Autoantigen; D009154:Mutation / Q000235:genetics*; D009492:Neurospora crassa / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*; D010641:Phenotype; D053484:RecQ Helicases; D011995:Recombination, Genetic; D013489:Suppression, Genetic
chemical_list: D034961:Antigens, Nuclear; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C083569:MEI-3 protein, Neurospora crassa; D004247:DNA; D000251:Adenosine Triphosphatases; C506725:RECQL protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; C402647:QDE-3 protein, Neurospora crassa