Work

Five dysfunctional telomeres predict onset of senescence in human cells

Year: 2011

Type: article

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.

Source: EMBO Reports

DOI: 10.1038/embor.2011.227

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

Institutions: The University of Sydney, Children's Medical Research Institute

Language: English

Topic: Telomeres, Telomerase, and Senescence

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $7,990