title: The type of mutations induced by carbon-ion-beam irradiation of the filamentous fungus Neurospora crassa.
abstract: Heavy-ion beams are known to cause great damage to cellular components and are particularly renowned for their ability to generate DNA double-strand breaks (DSBs). To gain insight into the mutagenic effect of carbon-ion beams and how such damage is repaired by the cell, Neurospora crassa mutants deficient in one of three components involved in the repair of DSBs, nonhomologous end-joining (NHEJ), homologous recombination repair (HR), and the Mre11-Rad50-Xrs2 (MRX) complex, were irradiated with a carbon-ion beam and killing effect, mutation frequencies, and the type of mutation incurred by survivors were analysed. The sensitivity of the NHEJ-deficient strain (mus-52) was higher than that of the wild-type and the HR-deficient (mei-3) strains at low doses of radiation, but was little changed as the level increased. As a result both the wild-type and HR-deficient strains were more sensitive than the NHEJ-deficient strain at high radiation levels. In addition, the frequency of forward mutation at the adenine-3 (ad-3) loci of the NHEJ-deficient mutant was lower than that of the wild-type strain at all levels, while the mutation frequency of the HR-deficient strain was consistently ∼3-fold higher than the wild-type. From the comparison of mutation type of each strain, deletions were frequently observed in wild-type strain, whilst base substitution and deletion in the mus-52 and mei-3 strains. These mutations resulting from carbon-ion-beam irradiation depend on the mechanism invoked to cope with DSBs. Furthermore, in wild-type cells, these mechanisms likely compete to repair DSBs.
authors.affiliation: Laboratory of Genetics, Department of Regulatory Biology, Faculty of Science, Saitama University, Shimo-okubo 255, Sakura ward, Saitama, Japan.
authors.forename: Liqiu
authors.initials: L
authors.lastname: Ma
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kazama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomoko
authors.initials: T
authors.lastname: Abe
authors.forename: Shin
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Shuuitsu
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D002244:Carbon; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D005658:Fungi / Q000235:genetics / Q000528:radiation effects; D007477:Ions; D050296:Microbial Viability / Q000528:radiation effects; D008969:Molecular Sequence Data; D009154:Mutation; D059645:Mutation Rate; D009492:Neurospora crassa / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects*; D011839:Radiation, Ionizing; D017422:Sequence Analysis, DNA
chemical_list: D004271:DNA, Fungal; D007477:Ions; D002244:Carbon