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  4. Telomere length homeostasis requires that telomerase levels are limiting
 
research article

Telomere length homeostasis requires that telomerase levels are limiting

Cristofari, G.
•
Lingner, J.  
2006
EMBO Journal

Stabilization of telomere length in germline and highly proliferative human cells is required for long-term survival and for the immortal phenotype of cancer-derived cells. This is achieved through expression of telomerase reverse transcriptase (TERT), which synthesizes telomeric repeats through reverse transcription of its tightly associated RNA template (TR). The telomeric repeat binding factor TRF1 inhibits telomerase at telomeres in cis in a length-dependent manner to achieve telomere length homeostasis. Here we manipulate telomerase activity over a wide range in cancer and primary cells. Concomitant overexpression of TERT and TR was necessary and sufficient to substantially increase telomerase activity. Upon overexpression, more telomerase associated with telomeres and telomeres elongated at a constant rate (up to 0.8 kb/population doubling (PD)) in a length-independent manner. Thus, in less than 50 PDs, the length of telomeres increased 3-8-fold beyond physiological size, while telomere-bound TRF1 and TRF2 increased proportionally to telomere length. Thus, long telomeres do not permanently adopt a structural state that is non-extendible. A low cellular concentration of telomerase is critical to achieve preferential elongation of short telomeres and telomere length homeostasis.

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Type
research article
DOI
10.1038/sj.emboj.7600952
Web of Science ID

WOS:000235803100012

Author(s)
Cristofari, G.
Lingner, J.  
Date Issued

2006

Published in
EMBO Journal
Volume

25

Issue

3

Start page

565

End page

574

Note

[1] Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland [2] Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland [3] National Center of Competence in Research 'Frontiers in Genetics', Switzerland.

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPLIN  
Available on Infoscience
November 20, 2007
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/14806
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