Long-lived organisms such as humans have evolved several intrinsic tumour suppressor mechanisms to combat the slew of oncogenic somatic mutations that constantly arise in proliferating stem-cell compartments. One of these anticancer barriers is the telomere, a specialized nucleoprotein complex that caps the ends of eukaryotic chromosome. Impaired telomere function activates the canonical DNA damage response pathway that engages p53 to initiate apoptosis or replicative senescence. Here, we discuss how p53-dependent senescence induced by dysfunctional telomeres may be as potent as apoptosis in suppressing tumorigenesis in vivo.
Bibliographical noteFunding Information:
S.C acknowledges generous financial support from the NIA (RO1 AG028888), the NCI (RO1 CA129037), the Welch Foundation, the Elsa U. Pardee Foundation, the Sydney Kimmel Foundation for Cancer Research, the Abraham and Phyllis Katz Foundation, and the Michael Kadoorie Cancer Genetic Research Program. Y.D. is supported by a NCI Howard Temin Award (1K01CA124461) and S.S.C is supported by a NIH Predoctoral Training Grant.