Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2009 Aug;11(8):988-93. doi: 10.1038/ncb1911. Epub 2009 Jul 13.

A two-step model for senescence triggered by a single critically short telomere.

Author information

  • 1LBMC, UMR 5239, CNRS- ENS Lyon, Université Lyon 1, Ecole Normale Supérieure, 46 allée d'Italie, F-69364 Lyon Cedex 07, France.

Erratum in

  • Nat Cell Biol. 2010 May;12(5):520.

Abstract

Telomeres protect chromosome ends from fusion and degradation. In the absence of a specific telomere elongation mechanism, their DNA shortens progressively with every round of replication, leading to replicative senescence. Here, we show that telomerase-deficient cells bearing a single, very short telomere senesce earlier, demonstrating that the length of the shortest telomere is a major determinant of the onset of senescence. We further show that Mec1p-ATR specifically recognizes the single, very short telomere causing the accelerated senescence. Strikingly, before entering senescence, cells divide for several generations despite complete erosion of their shortened telomeres. This pre-senescence growth requires RAD52 (radiation sensitive) and MMS1 (methyl methane sulfonate sensitive), and there is no evidence for major inter-telomeric recombination. We propose that, in the absence of telomerase, a very short telomere is first maintained in a pre-signalling state by a RAD52-MMS1-dependent pathway and then switches to a signalling state leading to senescence through a Mec1p-dependent checkpoint.

PMID:
19597486
[PubMed - indexed for MEDLINE]
PMCID:
PMC4025917
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk