+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Reversibility of replicative senescence inSaccharomyces cerevisiae Effect of homologous recombination and cell cycle checkpoints



Reversibility of replicative senescence inSaccharomyces cerevisiae Effect of homologous recombination and cell cycle checkpoints







Primary human somatic cells grown in culture divide a finite number of times, exhibiting progressive changes in metabolism and morphology before cessation of cycling. This telomere-initiated cellular senescence occurs because cells have halted production of telomerase, a DNA polymerase required for stabilization of chromosome ends. Telomerase-deficientSaccharomyces cerevisiaecells undergo a similar process, with most cells arresting growth after approximately 6 generations. In the current study we demonstrate that senescence is largely reversible. Reactivation of telomerase (EST2) expression in the growth-arrested cells led to resumption of cycling and reversal of senescent cell characteristics. Rescue was also observed after mating of senescent haploid cells with telomerase-proficient cells to form stable diploids. Although senescence was reversible in DNA damage checkpoint response mutants (mec3and/orrad24cells), survival of recombination-defectiverad52mutants remained low after telomerase reactivation. Telomere lengths in rescuedest2cells were initially half those of wildtype cells, but could be restored to normal by propagation for ?7 generations in the presence of telomerase. These results place limitations on possible models for senescence and indicate that most cells, despite gross morphological changes and short, resected telomeres, do not experience lethal DNA damage and become irreversibly committed to death.Reversibility of senescence in yeast cells was tested using two approaches. Despite telomere damage, most cells were viable after telomerase reactivation. Mating of senescent cells with normal cells also restored growth capability. Rescue by telomerase differed in checkpoint mutants and recombination mutants. Cells rescued by telomerase exhibited shortened telomeres..

Accession: 036255062

Download citation: RISBibTeXText


Related references

Reversibility of replicative senescence in Saccharomyces cerevisiae: effect of homologous recombination and cell cycle checkpoints. Dna Repair 11(1): 35-45, 2012

Replicative senescence and oxidant-induced premature senescence. Beyond the control of cell cycle checkpoints. Annals of the new York Academy of Sciences 908: 111-125, 2000

Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression and therapy resistance. Toxicology 193(1-2): 91-109, 2003

Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proceedings of the National Academy of Sciences of the United States of America 109(29): 11800, 2012

Cell cycle regulation of homologous recombination in Saccharomyces cerevisiae. Fems Microbiology Reviews 38(2): 172-184, 2014

Replication stress as a source of telomere recombination during replicative senescence in Saccharomyces cerevisiae. Fems Yeast Research 16(7):, 2016

Homologous recombination in the replicative cycle of adenovirus and its relationship to DNA replication. Current Topics in Microbiology and Immunology 199: 89-108, 1995

Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination: homologous recombination tolerates replicative stress by Mrc1-regulated replication and repair activities operating at S and G2 in distinct subnuclear compartments. Bioessays 36(5): 451-462, 2014

Sequence-dependent prediction of recombination hotspots inSaccharomyces cerevisiae. 2011

P53 Promotes cell survival due to the reversibility of its cell-cycle checkpoints. Molecular Cancer Research 13(1): 16-28, 2015

Characterization of ATM expression in cell cycle checkpoints and cellular senescence. Proceedings of the American Association for Cancer Research Annual Meeting 38: 157, 1997

PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science 270(5233): 50-51, 1995

Premature senescence or cell death Cell cycle checkpoints determine cellular response of normal human fibroblasts to oxidants. In Vitro Cellular and Developmental Biology Animal 38(Abstract): 8 A, Spring, 2002

DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis. Journal of Zhejiang University. Science. B 8(6): 377-397, 2007