RRC ID 27316
Author Nakamura T, Pluskal T, Nakaseko Y, Yanagida M.
Title Impaired coenzyme A synthesis in fission yeast causes defective mitosis, quiescence-exit failure, histone hypoacetylation and fragile DNA.
Journal Open Biol
Abstract Biosynthesis of coenzyme A (CoA) requires a five-step process using pantothenate and cysteine in the fission yeast Schizosaccharomyces pombe. CoA contains a thiol (SH) group, which reacts with carboxylic acid to form thioesters, giving rise to acyl-activated CoAs such as acetyl-CoA. Acetyl-CoA is essential for energy metabolism and protein acetylation, and, in higher eukaryotes, for the production of neurotransmitters. We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis. The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation. Moreover, ppc1-537 mutant cells failed to restore proliferation from quiescence. Ppc1 is thus the product of a super-housekeeping gene. The ppc1-537 mutant showed combined synthetic lethal defects with five of six histone deacetylase mutants, whereas sir2 deletion exceptionally rescued the ppc1-537 phenotype. In synchronous cultures, ppc1-537 cells can proceed to the S phase, but lose viability during mitosis failing in sister centromere/kinetochore segregation and nuclear division. Additionally, double-strand break repair is defective in the ppc1-537 mutant, producing fragile broken DNA, probably owing to diminished histone acetylation. The CoA-supported metabolism thus controls the state of chromosome DNA.
Volume 2(9)
Pages 120117
Published 2012-9
DOI 10.1098/rsob.120117
PII rsob120117
PMID 23091701
PMC PMC3472395
MeSH Acetylation Amino Acid Sequence Cell Cycle Checkpoints Coenzyme A / biosynthesis* DNA Breaks, Double-Stranded DNA Repair DNA, Fungal / metabolism Genes, Fungal Histone Acetyltransferases / genetics Histone Acetyltransferases / metabolism Histone Deacetylases / genetics Histone Deacetylases / metabolism Histones / metabolism* Mitosis Molecular Sequence Data Mutation Peptide Synthases / chemistry Peptide Synthases / genetics Peptide Synthases / metabolism Radiation Tolerance Schizosaccharomyces / cytology* Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces / radiation effects Schizosaccharomyces pombe Proteins / chemistry Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism Ultraviolet Rays
IF 3.286
Times Cited 12
Yeast FY7507 FY7519