Replicative Senescence as an Intrinsic Tumor-Suppressor Mechanism

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