A switch-like dynamic mechanism for the initiation of replicative senescence

Qing He Zhang, Xiao Jun Tian, Feng Liu, Wei Wang

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Telomeres are specialized structures protecting chromosomes against genome instability. Telomeres shorten with cell division, and replicative senescence is induced when telomeres are badly eroded. Whereas TRF2 (telomeric-repeat binding factor 2), ATM (ataxia telangiectasia mutated) and p53 have been identified involved in senescence induction, how it is triggered remains unclear. Here, we propose an integrated model associating telomere loss with senescence trigger. We characterize the dynamics of telomere shorting and the p53-centered regulatory network. We show that senescence is initiated in a switch-like manner when both the shortest telomere becomes uncapped and the TRF2-ATM-p53-Siah1 positive feedback loop is switched on. This work provides a coherent picture of senescence induction in terms of telomere shortening and p53 activation.

Original languageEnglish (US)
Pages (from-to)4369-4374
Number of pages6
JournalFEBS Letters
Volume588
Issue number23
DOIs
StatePublished - Nov 28 2014
Externally publishedYes

Keywords

  • Bistable switch
  • Regulatory network
  • Replicative senescence
  • Telomere shortening
  • p53 activation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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