Telomere dysfunction and tumour suppression: the senescence connection

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Abstract
Telomeres are TTAGGG repetitive sequences that cap the ends of eukaryotic chromosomes. A core of telomere binding proteins, termed the shelterin complex, serve to protect telomeric ends. Critical telomere shortening or uncapping of telomere binding proteins results in telomere dysfunction. Dysfunctional telomeres activate a DNA damage response. In the setting of a competent p53 pathway, this initiates senescence and apoptotic programmes to inhibit tumorigenesis. In cells with mutant p53, dysfunctional telomeres promote genome instability and progression to cancer. Cellular senescence is as potent as apoptosis in suppressing spontaneous tumorigenesis in mouse models of telomere dysfunction.