Telomere recombination accelerates cellular aging in Saccharomyces cerevisiae
Xiao-Fen Chen1, Fei-Long Meng, Jin-Qiu Zhou
1The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Plos Genetics
|June 27, 2009
Summary
Telomere recombination in yeast accelerates cellular aging, significantly shortening lifespan. Telomerase is a superior pathway for maintaining yeast replicative lifespan and organismal survival.
Area of Science:
- Cellular and Molecular Biology
- Genetics and Genomics
- Aging Research
Background:
- Telomeres protect chromosome ends, crucial for cell stability.
- Telomerase is the primary telomere maintenance enzyme, but recombination pathways exist.
- Budding yeast (Saccharomyces cerevisiae) utilizes both telomerase and recombination, serving as a model for evolutionary studies.
Purpose of the Study:
- To investigate the impact of telomere recombination on cellular lifespan in yeast.
- To compare the efficiency of telomere maintenance pathways under natural selection.
- To understand the aging mechanisms in telomerase-null yeast survivors.
Main Methods:
- Studied telomerase-null, post-senescent type II survivors using homologous recombination for telomere replication.
- Assessed replicative lifespan and cellular morphology.
- Investigated the effects of calorie restriction, TOR1 deletion, Fob1p inactivation, and Sir2p over-expression.
- Monitored rDNA recombination and extra-chromosomal rDNA circle accumulation.
- Reintroduced telomerase activity to assess lifespan restoration.
Main Results:
- Type II survivors maintained chromosomal integrity but had a significantly reduced replicative lifespan.
- These survivors exhibited premature aging phenotypes, consistent with wild-type senescence.
- Calorie restriction and TOR1 deletion extended lifespan; Fob1p inactivation and Sir2p over-expression did not.
- RDNA recombination decreased, ruling out increased rDNA circles as the cause of aging.
- Telomerase reintroduction restored replicative lifespan despite heterogeneous telomeres.
Conclusions:
- Telomere recombination accelerates cellular aging in telomerase-null yeast.
- Telomerase is a more effective pathway for sustaining yeast replicative lifespan.
- This highlights the evolutionary advantage of telomerase in long-term organismal survival.
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Overview
Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.


