Replicative Senescence as an Intrinsic Tumor-Suppressor Mechanism

  • Sandy Chang


One feature of human carcinomas is their strikingly complex cytogenetic profiles. An important mechanism that can give rise to this level of genomic instability is the functional status of telomeres, the protein-DNA complexes that cap the ends of chromosomes. Telomeres serve to protect eukaryotic chromosomal ends from being recognized as damaged DNA, and growing evidence suggests that critically shortened (dysfunctional) telomeres may help initiate the onset of cancer. Dysfunctional telomeres potently engage the DNA damage response pathway, leading to the onset of cellular senescence when p53 is functional. However, in the absence of p53, dysfunctional telomeres can initiate cancer by promoting genomic instability. In this chapter, I will use mouse models to illustrate the interplay between telomere dysfunction and the development of carcinomas in the setting of an intact or mutated p53-dependent DDR pathway. Dysfunctional telomeres trigger senescence when p53 is functional, thereby protecting epithelial tissues from cancer progression. These results suggest that p53-dependent senescence, induced by dysfunctional telomeres, may be as potent as apoptosis in suppressing tumorigenesis in vivo.


Telomere Length Cellular Senescence Replicative Senescence Dicentric Chromosome Telomere Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Alternative lengthening of telomeres


Ataxia-telangiectasia mutated


Ataxia-telangiectasia and Rad3 related




DNA damage response


DNA double stranded breaks


Human diploid fibroblasts


Homologous recombination


Loss of heterozygosity


Murine double minute 2


Nonhomologous end joining


Nonreciprocal translocations


Fold-oligosaccharide/oligonucleotide-binding fold


Protection of telomeres 1


Senescence-associated β-galactosidase


Telomerase RNA template


Telomerase reverse transcriptase


TRF1 interacting protein 2


Telomeric-repeat binding factor 1


Telomeric-repeat binding factor 2


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Genetics, Unit 1006U.T.M.D. Anderson Cancer CenterHoustonUSA

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