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EMBO Rep. 2011 Dec 23;13(1):52-9. doi: 10.1038/embor.2011.227.

Five dysfunctional telomeres predict onset of senescence in human cells.

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1
Cancer Research Unit, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.

Abstract

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.

PMID:
22157895
PMCID:
PMC3246253
DOI:
10.1038/embor.2011.227
[Indexed for MEDLINE]
Free PMC Article
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