Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants.

Published

Journal Article

In addition to threonine auxotrophy, mutation of the Saccharomyces cerevisiae threonine biosynthetic genes THR1 (encoding homoserine kinase) and THR4 (encoding threonine synthase) results in a plethora of other phenotypes. We investigated the basis for these other phenotypes and found that they are dependent on the toxic biosynthetic intermediate homoserine. Moreover, homoserine is also toxic for Candida albicans thr1Delta mutants. Since increasing levels of threonine, but not other amino acids, overcome the homoserine toxicity of thr1Delta mutants, homoserine may act as a toxic threonine analog. Homoserine-mediated lethality of thr1Delta mutants is blocked by cycloheximide, consistent with a role for protein synthesis in this lethality. We identified various proteasome and ubiquitin pathway components that either when mutated or present in high copy numbers suppressed the thr1Delta mutant homoserine toxicity. Since the doa4Delta and proteasome mutants identified have reduced ubiquitin- and/or proteasome-mediated proteolysis, the degradation of a particular protein or subset of proteins likely contributes to homoserine toxicity.

Full Text

Duke Authors

Cited Authors

  • Kingsbury, JM; McCusker, JH

Published Date

  • May 2010

Published In

Volume / Issue

  • 9 / 5

Start / End Page

  • 717 - 728

PubMed ID

  • 20305002

Pubmed Central ID

  • 20305002

Electronic International Standard Serial Number (EISSN)

  • 1535-9786

Digital Object Identifier (DOI)

  • 10.1128/EC.00044-10

Language

  • eng

Conference Location

  • United States