Links between nucleolar activity, rDNA stability, aneuploidy and chronological aging in the yeast Saccharomyces cerevisiae.
The nucleolus is speculated to be a regulator of cellular senescence in numerous biological systems (Guarente, Genes Dev 11(19):2449-2455, 1997; Johnson et al., Curr Opin Cell Biol 10(3):332-338, 1998). In the budding yeast Saccharomyces cerevisiae, alterations in nucleolar architecture, the redistribution of nucleolar protein and the accumulation of extrachromosomal ribosomal DNA circles (ERCs) during replicative aging have been reported. However, little is known regarding rDNA stability and changes in nucleolar activity during chronological aging (CA), which is another yeast aging model used. In the present study, the impact of aberrant cell cycle checkpoint control (knock-out of BUB1, BUB2, MAD1 and TEL1 genes in haploid and diploid hemizygous states) on CA-mediated changes in the nucleolus was studied. Nucleolus fragmentation, changes in the nucleolus size and the nucleolus/nucleus ratio, ERC accumulation, expression pattern changes and the relocation of protein involved in transcriptional silencing during CA were revealed. All strains examined were affected by oxidative stress, aneuploidy (numerical rather than structural aberrations) and DNA damage. However, the bub1 cells were the most prone to aneuploidy events, which may contribute to observed decrease in chronological lifespan. We postulate that chronological aging may be affected by redox imbalance-mediated chromosome XII instability leading to both rDNA instability and whole chromosome aneuploidy. CA-mediated nucleolus fragmentation may be a consequence of nucleolus enlargement and/or Nop2p upregulation. Moreover, the rDNA content of chronologically aging cells may be a factor determining the subsequent replicative lifespan. Taken together, we demonstrated that the nucleolus state is also affected during CA in yeast.
Department of Biochemistry and Cell Biology, University of Rzeszow, Rzeszow, Poland.
Anna
A
Lewinska
Beata
B
Miedziak
Klaudia
K
Kulak
Mateusz
M
Molon
Maciej
M
Wnuk
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000782:Aneuploidy; D018797:Cell Cycle Proteins / Q000235:genetics; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D000089804:Shelterin Complex; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C070351:BUB2 protein, S cerevisiae; C584280:Bub1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004275:DNA, Ribosomal; D047908:Intracellular Signaling Peptides and Proteins; C501382:MAD1 protein, S cerevisiae; C077734:NPL3 protein, S cerevisiae; D009687:Nuclear Proteins; C440829:RAP1 protein, S cerevisiae; D016601:RNA-Binding Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae