Five dysfunctional telomeres predict onset of senescence in human cells |
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Authors: | Kaul Zeenia Cesare Anthony J Huschtscha Lily I Neumann Axel A Reddel Roger R |
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Affiliation: | Cancer Research Unit, Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia. |
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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. |
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Keywords: | telomeres DNA damage response senescence |
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