NEM1 acts as a suppressor of apoptotic phenotypes in LSM4 yeast mutants.

Saccharomyces cerevisiae mutants in the essential gene LSM4, involved in messenger RNA decapping, and expressing a truncated form of the LSM4 gene of the yeast Kluyveromyces lactis (Kllsm4Δ1), show premature aging accompanied by the presence of typical markers of apoptosis and high sensitivity to oxidative stressing agents. We isolated multicopy extragenic suppressors of these defects, transforming the Kllsm4Δ1 mutant with a yeast DNA library and selecting clones showing resistance to acetic acid. Here we present one of these clones, carrying a DNA fragment containing the NEM1 gene (Nuclear Envelope Morphology protein 1), which encodes the catalytic subunit of the Nem1p-Spo7p phosphatase holoenzyme.

PGK1, the gene encoding the glycolitic enzyme phosphoglycerate kinase, acts as a multicopy suppressor of apoptotic phenotypes in S. cerevisiae.

In a previous paper we reported the construction of a S. cerevisiae strain lacking the essential gene LSM4, which could survive by the introduction of a truncated form of the orthologous gene from Kluyveromyces lactis. This strain showed apoptotic hallmarks and other phenotypes, including an increased sensitivity to caffeine and acetic acid.

HIR1, the co-repressor of histone gene transcription of Saccharomyces cerevisiae, acts as a multicopy suppressor of the apoptotic phenotypes of the LSM4 mRNA degradation mutant.

We previously have reported that Saccharomyces cerevisiae mutants expressing Kllsm4Delta1, a truncated form of the KlLSM4 gene, as well as mutants in genes of the mRNA-decapping pathway, show phenotypic markers of apoptosis, increased temperature sensitivity and reduced growth in the presence of different drugs and oxidative stressing agents, such as acetic acid and H(2)O(2). To isolate multicopy extra-genic suppressors of these defects, we transformed the Kllsm4Delta1 mutant with a yeast DNA library and we selected a series of clones showing resistance to acetic acid. One of these clones carried a DNA fragment containing the HIR1 gene that encodes a transcriptional co-repressor of histone genes.