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.
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.
Kato
Akihiro
A
Laboratory of Genetics, Department of Regulation Biology, Faculty of Science, Saitama University, 338-8570 Saitama, Japan.
Inoue
Hirokazu
H
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
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