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Five dysfunctional telomeres predict onset of senescence in human cells.

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.

SUBMITTER: Kaul Z

PROVIDER: S-EPMC3246253 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Five dysfunctional telomeres predict onset of senescence in human cells.

Kaul Zeenia Z Cesare Anthony J AJ Huschtscha Lily I LI Neumann Axel A AA Reddel Roger R RR

EMBO reports 20111223 1

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 ...[more]

PMID: 22157895

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