title: Hypomorphic bimA(APC3) alleles cause errors in chromosome metabolism that activate the DNA damage checkpoint blocking cytokinesis in Aspergillus nidulans.
abstract: The Aspergillus nidulans sepI(+) gene has been implicated in the coordination of septation with nuclear division and cell growth. We find that the temperature-sensitive (ts) sepI1 mutation represents a novel allele of bimA(APC3), which encodes a conserved component of the anaphase-promoting complex/cyclosome (APC/C). We have characterized the septation, nuclear division, cell-cycle checkpoint defects, and DNA sequence alterations of sepI1 (renamed bimA10) and two other ts lethal bimA(APC3) alleles, bimA1 and bimA9. Our observations that bimA9 and bimA10 strains had morphologically abnormal nuclei, chromosome segregation defects, synthetic phenotypes with mutations in the DNA damage checkpoint genes uvsB(MEC1/rad3) or uvsD(+), and enhanced sensitivity to hydroxyurea strongly suggest that these strains accumulate errors in DNA metabolism. We found that the aseptate phenotype of bimA9 and bimA10 strains was substantially relieved by mutations in uvsB(MEC1/rad3) or uvsD(+), suggesting that the presence of a functional DNA damage checkpoint inhibits septation in these bimA(APC3) strains. Our results demonstrate that mutations in bimA(APC3) lead to errors in DNA metabolism that indirectly block septation.
authors.affiliation: Department of Biology, Purdue University, West Lafayette, Indiana 47907-1392, USA. wolkow@rascal.med.harvard.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Wolkow
authors.forename: P M
authors.initials: PM
authors.lastname: Mirabito
authors.forename: S
authors.initials: S
authors.lastname: Venkatram
authors.forename: J E
authors.initials: JE
authors.lastname: Hamer
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000166:cytology / Q000235:genetics*; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D015825:Chromosomes, Fungal; D004249:DNA Damage / Q000235:genetics*; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D004271:DNA, Fungal; D005656:Fungal Proteins; D009687:Nuclear Proteins; C072411:BIMA protein, Emericella nidulans