Mutations synthetically lethal with tpm1delta lie in genes involved in morphogenesis.
Yeast contains two genes, TPM1 and TPM2, encoding tropomyosins, either of which can provide an essential function in the yeast cytoskeleton. To elucidate more clearly the function of the major tropomyosin, encoded by TPM1, we have isolated mutations that confer synthetic lethality with the null mutant of TPM1. Here we describe a phenotypic and genetic analysis of mutations in TSL1/BEM2, TSL2, TSL3, TSL5, and TSL6 (tropomyosin synthetic lethal). All the mutants exhibit clear morphological and some actin cytoskeletal defects, but are not noticeably defective in secretion, endocytosis, or organelle segregation. The lethality conferred by tsl tpm1delta mutations could be specifically suppressed by either TPM1 or an additional copy of TPM2. This implies that the essential function compromised in the tsl tpm1delta constructs is the same essential function for which Tpm1p or Tpm2p is necessary. Synthetic interactions and unlinked noncomplementation were observed between the tsl mutants, suggesting that they participate in related functions involving morphogenesis. In support of this, tsl6-1 was identified as an allele of the nonessential gene SLT2 or MPK1 whose product is a MAP kinase regulating cell wall synthesis. These results indicate that this synthetic lethality approach provides a sensitive screen for the isolation of mutations affecting morphogenesis, many of which are likely to be in nonessential genes, like BEM2 and SLT2.
Wang
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T
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA.
Bretscher
A
A
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus; D003599:Cytoskeleton; D004705:Endocytosis; D005656:Fungal Proteins / Q000235:genetics; D020690:GTPase-Activating Proteins; D005800:Genes, Fungal; D005804:Genes, Lethal; D005813:Genes, Synthetic; D005816:Genetic Complementation Test; D009024:Morphogenesis / Q000235:genetics; D016296:Mutagenesis; D015388:Organelles; D010641:Phenotype; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D014335:Tropomyosin / Q000235:genetics* / Q000502:physiology
D000199:Actins; C084219:BEM2 protein, S cerevisiae; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014335:Tropomyosin