RRC ID 54631
Author Tanabe T, Yamaga M, Kawamukai M, Matsuo Y.
Title Mal3 is a multi-copy suppressor of the sensitivity to microtubule-depolymerizing drugs and chromosome mis-segregation in a fission yeast pka1 mutant.
Journal PLoS One
Abstract The cAMP-dependent protein kinase Pka1 is known as a regulator of glycogenesis, transition into meiosis, chronological aging, and stress responses in the fission yeast, Schizosaccharomyces pombe. We demonstrated here that Pka1 is responsible for normal growth in the presence of the microtubule-destabilization drug TBZ and proper chromosome segregation. The deletion of the pka1 gene resulted in the TBZ-sensitive phenotype and chromosome mis-segregation. We isolated the mal3 gene as a multi-copy suppressor of the TBZ-sensitive phenotype in the pka1Δ strains. Overexpression of the CH domain (1-143) or the high-affinity microtubule binding mutant (1-143 Q89R) of Mal3 rescued the TBZ-sensitive phenotype in the pka1Δ and mal3Δ strains, while the EB1 domain (135-308) and the mutants defective in microtubule binding (1-143 Q89E) failed to do so in the same strains. Chromosome mis-segregation caused by TBZ in the pka1Δ or mal3Δ strains was suppressed by the overexpression of the Mal3 CH domain (1-143), Mal3 CH domain with the coiled-coil domain (1-197), or full-length Mal3. Overexpression of EB1 orthologs from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, or Homo sapiens suppressed the TBZ-sensitive phenotype in the pka1Δ strains, indicating their conserved functions. These findings suggest that Pka1 and the microtubule binding of the Mal3 CH domain play a role in the maintenance of proper chromosome segregation.
Volume 14(4)
Pages e0214803
Published 2019-1-1
DOI 10.1371/journal.pone.0214803
PII PONE-D-18-25545
PMID 30973898
PMC PMC6459531
MeSH Animals Chromosome Segregation Cyclic AMP-Dependent Protein Kinases / genetics* Cyclic AMP-Dependent Protein Kinases / metabolism* Genes, Fungal Genes, Suppressor Humans Mice Microtubule-Associated Proteins / chemistry Microtubule-Associated Proteins / genetics* Microtubule-Associated Proteins / metabolism Microtubules / drug effects Microtubules / metabolism Mutation Phenotype Protein Domains Schizosaccharomyces / drug effects Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / genetics* Schizosaccharomyces pombe Proteins / metabolism* Tubulin Modulators / pharmacology
IF 2.776
Times Cited 1
Yeast FY8144