Control of telomere length by the human telomeric protein TRF1

Bas van Steensel and Titia de Lange
Additional contact information
Bas van Steensel: The Rockefeller University
Titia de Lange: The Rockefeller University

Nature, 1997, vol. 385, issue 6618, 740-743

Abstract: Abstract Human telomeres, the nucleoprotein complexes at chromosome ends, consist of tandem arrays of TTAGGG repeats bound to specific proteins. In normal human cells, telomeres shorten with successive cell divisions1,2, probably due to the terminal sequence loss that accompanies DNA replication. In tumours and immortalized cells, this decline is halted through the activation of telomerase3–5, a reverse transcriptase that extends the telomeric TTAGGG-repeat arrays6–7. Telomere length is stable in several immortal human-cell lines3, suggesting that a regulatory mechanism exists for limiting telomere elongation by telomerase. Here we show that the human telomeric-repeat binding factor TRF1 (ref. 8) is involved in this regulation. Long-term overexpression of TRF1 in the telomerase-positive tumour-cell line HT1080 resulted in a gradual and progressive telomere shortening. Conversely, telomere elongation was induced by expression of a dominant-negative TRF1 mutant that inhibited binding of endogenous TRF1 to telomeres. Our results identify TRF1 as a suppressor of telomere elongation and indicate that TRF1 is involved in the negative feedback mechanism that stabilizes telomere length. As TRF1 does not detectably affect the expression of telomerase, we propose that the binding of TRF1 controls telomere length in cis by inhibiting the action of telomerase at the ends of individual telomeres.

Date: 1997
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/385740a0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:385:y:1997:i:6618:d:10.1038_385740a0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/385740a0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().