Details

Autor(en) / Beteiligte

• Kaul, Zeenia
• Cesare, Anthony J
• Huschtscha, Lily I
• Neumann, Axel A
• Reddel, Roger R

Titel

Five dysfunctional telomeres predict onset of senescence in human cells

Ist Teil von

• EMBO reports, 2012-01, Vol.13 (1), p.52-59

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Replicative senescence is accompanied by a telomere‐specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early‐passage normal human cells and increase in number with increasing cumulative cell divisions. DDR+ telomeres at replicative senescence retain TRF2 and RAP1 proteins, are not associated with end‐to‐end fusions and mostly result from strand‐independent, postreplicative dysfunction. On the basis of the calculated number of DDR+ telomeres in G1‐phase cells just before senescence and after bypassing senescence by inactivation of wild‐type p53 function, we conclude that the accrual of five telomeres in G1 that are DDR+ but nonfusogenic is associated with p53‐dependent senescence. Replicative senescence is triggered by DNA damage response foci associated with telomeres. Reddel and colleagues now establish that a threshold of five damaged telomeres exists to induce senescence in normal cells and that end‐to‐end chromosome fusion is not required for senescence induction.