title: Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer.
abstract: The ends of eukaryotic chromosomes are protected by specialized structures termed telomeres that serve in part to prevent the chromosome end from activating a DNA damage response. However, this important function for telomeres in chromosome end protection can be lost as telomeres shorten with cell division in culture or in self-renewing tissues with advancing age. Impaired telomere function leads to induction of a DNA damage response and activation of the tumor suppressor protein p53. p53 serves a critical role in enforcing both senescence and apoptotic responses to dysfunctional telomeres. Loss of p53 creates a permissive environment in which critically short telomeres are inappropriately joined to generate chromosomal end-to-end fusions. These fused chromosomes result in cycles of chromosome fusion-bridge-breakage, which can fuel cancer initiation, especially in epithelial tissues, by facilitating changes in gene copy number.
authors.affiliation: Department of Medicine, Division of Hematology and Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA. sartandi@stanford.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Artandi
authors.forename: Laura D
authors.initials: LD
authors.lastname: Attardi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D043171:Chromosomal Instability / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D016193:G1 Phase; D016158:Genes, p53; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology*; D015398:Signal Transduction; D019098:Telomerase / Q000502:physiology; D016615:Telomere / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D019098:Telomerase