title: The human telomere-associated protein TIN2 stimulates interactions between telomeric DNA tracts in vitro.
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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Sahn-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Seungil
authors.initials: S
authors.lastname: Han
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: You
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D004247:DNA / Q000235:genetics / Q000378:metabolism*; D015342:DNA Probes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015342:DNA Probes; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D004247:DNA