Systematic exploration of essential yeast gene function with temperature-sensitive mutants

Nat Biotechnol. 2011 Apr;29(4):361-7. doi: 10.1038/nbt.1832. Epub 2011 Mar 27.

Abstract

Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (∼45%) of the 1,101 essential yeast genes, with ∼30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)-based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Databases, Genetic
  • Genes, Essential*
  • Genes, Fungal
  • Genes, Lethal
  • Genetic Engineering / methods
  • Genetic Loci
  • Genome, Fungal*
  • Mass Spectrometry / methods
  • Microarray Analysis / methods
  • Microscopy, Confocal
  • Mutation
  • Phenotype
  • Plasmids
  • RNA, Messenger
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Single-Cell Analysis
  • Temperature*
  • Tubulin / analysis

Substances

  • RNA, Messenger
  • Tubulin