title: Mitotic catastrophe is the mechanism of lethality for mutations that confer mutagen sensitivity in Aspergillus nidulans.
abstract: We have examined the consequences of treatment with DNA-damaging agents of uvs mutants and the bimD6 mutant of Aspergillus nidulans. We first established that wild-type Aspergillus undergoes a cell cycle delay following treatment with the DNA-damaging agents methyl methanesulfonate (MMS) or ultraviolet light (UV). We have also determined that strains carrying the bimD6, uvsB110, uvsH77, uvsF201 and the uvsC114 mutations, all of which cause an increased sensitivity to DNA-damaging agents, undergo a cell-cycle delay following DNA damage. These mutations therefore do not represent nonfunctional checkpoints in Aspergillus. However, all of the mutant strains accumulated nuclear defects after a period of delay following mutagen treatment. The nuclear defects in the uvsB110 and bimD6 strains following MMS treatment were shown to be dependent on passage through mitosis after DNA damage, as the defects were prevented with benomyl. Checkpoint controls responding to DNA damage thus only temporarily halt cell-cycle progression in response to DNA damage. The conditional bimD6 mutation also results in a defective mitosis at restrictive temperatures. This mitotic defect is similar to that seen with MMS treatment at temperatures permissive for the mitotic defect. Thus the bimD gene product may perform dual roles, one in DNA repair and the other during the mitotic cell cycle in the absence of damage.
authors.affiliation: Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: S H
authors.initials: SH
authors.lastname: Denison
authors.forename: G S
authors.initials: GS
authors.lastname: May
mesh_terms: D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D016923:Cell Death; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004361:Drug Tolerance; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal / Q000235:genetics* / Q000502:physiology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008938:Mitosis / Q000502:physiology*; D009154:Mutation; D011836:Radiation Tolerance; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: C083254:BIMD protein, Emericella nidulans; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D008741:Methyl Methanesulfonate