Telomere cap components influence the rate of senescence in telomerase-deficient yeast cells.
Cells lacking telomerase undergo senescence, a progressive reduction in cell division that involves a cell cycle delay and culminates in "crisis," a period when most cells become inviable. In telomerase-deficient Saccharomyces cerevisiae cells lacking components of the nonsense-mediated mRNA decay (NMD) pathway (Upf1,Upf2, or Upf3 proteins), senescence is delayed, with ... crisis occurring approximately 10 to 25 population doublings later than in Upf+ cells. Delayed senescence is seen in upfDelta cells lacking the telomerase holoenzyme components Est2p and TLC1 RNA, as well as in cells lacking the telomerase regulators Est1p and Est3p. The delay of senescence in upfDelta cells is not due to an increased rate of survivor formation. Rather, it is caused by alterations in the telomere cap, composed of Cdc13p, Stn1p, and Ten1p. In upfDelta mutants, STN1 and TEN1 levels are increased. Increasing the levels of Stn1p and Ten1p in Upf+ cells is sufficient to delay senescence. In addition, cdc13-2 mutants exhibit delayed senescence rates similar to those of upfDelta cells. Thus, changes in the telomere cap structure are sufficient to affect the rate of senescence in the absence of telomerase. Furthermore, the NMD pathway affects the rate of senescence in telomerase-deficient cells by altering the stoichiometry of telomere cap components.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Base Sequence, Cell Cycle, Cell Cycle Proteins, Cell Division, Codon, Nonsense, DNA, Fungal, DNA-Binding Proteins, Fungal Proteins, Genes, Fungal, Models, Biological, Mutation, Proteins, RNA Helicases, RNA, Fungal, RNA, Messenger, RNA-Binding Proteins, Rad52 DNA Repair and Recombination Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomerase, Telomere, Telomere-Binding Proteins, Trans-Activators
Adaptor Proteins, Signal Transducing, Base Sequence, Cell Cycle, Cell Cycle Proteins, Cell Division, Codon, Nonsense, DNA, Fungal, DNA-Binding Proteins, Fungal Proteins, Genes, Fungal, Models, Biological, Mutation, Proteins, RNA Helicases, RNA, Fungal, RNA, Messenger, RNA-Binding Proteins, Rad52 DNA Repair and Recombination Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomerase, Telomere, Telomere-Binding Proteins, Trans-Activators
Mol. Cell. Biol.
Date: Jan. 01, 2004
PubMed ID: 14701754
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