Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2

We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere sh...

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Vydáno v:Molecular and cellular biology Ročník 22; číslo 10; s. 3474
Hlavní autoři: Ancelin, Katia, Brunori, Michele, Bauwens, Serge, Koering, Catherine-Elaine, Brun, Christine, Ricoul, Michelle, Pommier, Jean-Patrick, Sabatier, Laure, Gilson, Eric
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.05.2002
Témata:
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Cell Line
Chromosomes - genetics
Chromosomes - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Escherichia coli Proteins
Humans
In Situ Hybridization, Fluorescence
Lac Repressors
Nuclear Proteins - metabolism
Recombinant Fusion Proteins - metabolism
Repressor Proteins - genetics
Repressor Proteins - metabolism
Telomerase - metabolism
Telomere - metabolism
Telomeric Repeat Binding Protein 1
Telomeric Repeat Binding Protein 2
Transfection
ISSN:0270-7306
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Popis
Shrnutí:We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. Inhibition of telomerase activity by a modified oligonucleotide did not further increase the pace of telomere erosion caused by TRF1 targeting, suggesting that telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting and telomerase inhibition have additive effects. The possibility that TRF2 can activate a telomeric degradation pathway was directly tested in human primary cells that do not express telomerase. In these cells, overexpression of full-length TRF2 leads to an increased rate of telomere shortening.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0270-7306
DOI:10.1128/MCB.22.10.3474-3487.2002