4.4 Article

Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing

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CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2014.06.009

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资金

  1. Fondazione Italiana per la Ricerca sul Cancro (FIRC) [12476]
  2. NIH/NCI [R01CA136533]
  3. Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG11407]
  4. Cofinanziamento MIUR/Universita di Milano-Bicocca
  5. FIRC
  6. AIRC [12971]
  7. AICR [14-1331]
  8. HFSP (Human Frontier Science Program) [RGP 0014/2012]
  9. Cariplo Foundation [2010.0818]
  10. FP7 PEOPLE ITN (CodAge)
  11. Telethon [GGP12059]
  12. PRIN
  13. European Research Council [322726]
  14. EPIGEN project (an initiative of the Italian Ministry of Education, University and Research)
  15. EPIGEN project (an initiative of the National Research Council)

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The DNA damage response (DDR) orchestrates DNA repair and halts cell cycle. If damage is not resolved, cells can enter into an irreversible state of proliferative arrest called cellular senescence. Organismal ageing in mammals is associated with accumulation of markers of cellular senescence and DDR persistence at telomeres. Since the vast majority of the cells in mammals are non-proliferating, how do they age? Are telomeres involved? Also oncogene activation causes cellular senescence due to altered DNA replication and DDR activation in particular at the telomeres. Is there a common mechanism shared among apparently distinct types of cellular senescence? And what is the role of telomeric DNA damage?

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