MUTATIONS SYNTHETICALLY LETHAL WITH TPM1-DELTA 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, enco ded by TPM1, we have isolated mutations that confer synthetic lethalit y with the null mutant of TPM1. Here we describe a phenotypic and gene tic analysis of mutations in TSL1/BEM2, TSL2, TSL3 TSL5, and TSL6 (tro pomyosin synthetic lethal). All the mutants exhibit clear morphologica l and some actin cytoskeletal defects, but are not noticeably defectiv e in secretion, endocytosis, or organelle segregation. The lethality c onferred by tsl tpm1 Delta mutations could be specifically suppressed by either TPM1 or an additional copy of TPM2. This implies that the es sential function compromised in the tsl tpm1 Delta constructs is the s ame essential function for which Tpm1p or Tpm2p is necessary. Syntheti c interactions and unlinked noncomplementation were observed between t he tsl mutants, suggesting that they participate in related functions involving morphogenesis. In support of this, tsl6-I 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 th is synthetic lethality approach provides a sensitive screen for the is olation of mutations affecting morphogenesis, many of which are likely to be in nonessential genes, like BEM2 and SLT2.