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. The over-expression of HIR1 in the Kllsm4Delta1 mutant prevented rapid cell death during chronological aging, reduced nuclei fragmentation and increased resistance to H(2)O(2). Transcription analysis revealed that the expression of histone genes was lowered in the mutant over-expressing HIR1, indicating a relationship between the latter gene and apoptosis.
Mazzoni
Cristina
C
Pasteur Institute-Cenci Bolognetti Foundation, Department of Cell and Developmental Biology, University of Rome La Sapienza, Piazzale Aldo Moro 5, Italy. cristina.mazzoni@uniroma1.it
Palermo
Vanessa
V
Torella
Mirko
M
Falcone
Claudio
C
D019342:Acetic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis; D016922:Cellular Senescence; D053938:DNA Fragmentation; D025141:Drug Resistance, Fungal; D017353:Gene Deletion; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015723:Gene Library; D005816:Genetic Complementation Test; D006657:Histones / Q000235:genetics; D006861:Hydrogen Peroxide / Q000633:toxicity; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012331:RNA, Fungal / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology*; D013489:Suppression, Genetic
D000935:Antifungal Agents; C078808:HIR1 protein, S cerevisiae; D006657:Histones; C093543:LSM4 protein, S cerevisiae; D009687:Nuclear Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D019342:Acetic Acid