Activation of the DNA damage response by telomere attrition: a passage to cellular senescence.
Critical telomere shortening induces senescence in many normal human cell types grown in culture. Recent data have revealed that dysfunctional telomeres can resemble certain forms of DNA damage, and point to a role for DNA damage signaling in the establishment and maintenance of telomere-initiated senescence. Here, we review these new observations and highlight potential avenues of future research. We consider the identities of the key DNA damage response factors involved in senescence and discuss a model for the molecular events occurring in pre-senescent cells that ultimately lead to a permanent cell cycle arrest phenotype.
Reaper
Philip M
PM
The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, UK.
di Fagagna
Fabrizio d'Adda
Fd
Jackson
Stephen P
SP
D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006801:Humans; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019098:Telomerase