The human telomere-associated protein TIN2 stimulates interactions between telomeric DNA tracts in vitro

Sahn Ho Kim, Seungil Han, Young Hyun You, David J. Chen, Judith Campisi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Human TIN2 interacts with the telomeric-DNA-binding protein TRF1, suppresses telomere elongation in telomerase-positive cells, and may control telomere length by modulating telomere structure. To test the latter idea, we developed an in vitro assay, using biotinylated telomeric DNA probes and streptavidin-agarose, to quantify the ability of TRF1 and TIN2 to stimulate interactions of telomeric DNA tracts with each other (probe clustering). This assay revealed that TRF1 alone had weak probe-clustering activity, but TIN2 stimulated activity fivefold to tenfold. A dominant-negative TIN2 mutant protein that increased telomere length in vivo disrupted probe clusters formed by TRF1 and TIN2, suggesting that the ability to stimulate telomeric DNA interactions is important for telomere-length regulation. Unlike TRF1, TIN2 did not form homodimers. We propose that TIN2 alters the conformation of TRF1, which favours a tertiary telomeric structure that hinders telomerase from gaining access to telomeres.

Original languageEnglish (US)
Pages (from-to)685-691
Number of pages7
JournalEMBO Reports
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2003

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Telomere
Telomerase
Assays
DNA
DNA Probes
DNA-Binding Proteins
Mutant Proteins
Cluster Analysis
Conformations
Elongation
Cells
human TINF2 protein
In Vitro Techniques

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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The human telomere-associated protein TIN2 stimulates interactions between telomeric DNA tracts in vitro. / Kim, Sahn Ho; Han, Seungil; You, Young Hyun; Chen, David J.; Campisi, Judith.

In: EMBO Reports, Vol. 4, No. 7, 01.07.2003, p. 685-691.

Research output: Contribution to journalArticle

Kim, Sahn Ho ; Han, Seungil ; You, Young Hyun ; Chen, David J. ; Campisi, Judith. / The human telomere-associated protein TIN2 stimulates interactions between telomeric DNA tracts in vitro. In: EMBO Reports. 2003 ; Vol. 4, No. 7. pp. 685-691.
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