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Senescence Induced by Altered Telomere State, Not Telomere Loss

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Science  29 Mar 2002:
Vol. 295, Issue 5564, pp. 2446-2449
DOI: 10.1126/science.1069523

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Abstract

Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.

  • * To whom correspondence should be addressed. E-mail: delange{at}mail.rockefeller.edu

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