Hypomorphic bimA^APC3 Alleles Cause Errors in Chromosome Metabolism That Activate the DNA Damage Checkpoint Blocking Cytokinesis in Aspergillus nidulans

Corresponding author: Tom D. Wolkow, Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115., wolkow{at}rascal.med.harvard.edu (E-mail)

Communicating editor: R. H. DAVIS

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.

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