Direct single-stranded DNA binding by Teb1 mediates the recruitment of Tetrahymena thermophila telomerase to telomeres.

Autor:	Upton HE; Department of Molecular and Cell Biology, University of California, Berkeley, California, USA., Hong K; Department of Molecular and Cell Biology, University of California, Berkeley, California, USA., Collins K; Department of Molecular and Cell Biology, University of California, Berkeley, California, USA kcollins@berkeley.edu.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2014 Nov 15; Vol. 34 (22), pp. 4200-12. Date of Electronic Publication: 2014 Sep 15.
DOI:	10.1128/MCB.01030-14
Abstrakt:	The eukaryotic reverse transcriptase telomerase copies its internal RNA template to synthesize telomeric DNA repeats at chromosome ends in balance with sequence loss during cell proliferation. Previous work has established several factors involved in telomerase recruitment to telomeres in yeast and mammalian cells; however, it remains unclear what determines the association of telomerase with telomeres in other organisms. Here we investigate the cell cycle dependence of telomere binding by each of the seven Tetrahymena thermophila telomerase holoenzyme proteins TERT, p65, Teb1, p50, p75, p45, and p19. We observed coordinate cell cycle-regulated recruitment and release of all of the subunits, including the telomeric-repeat DNA-binding subunit Teb1. Using domain truncation and mutagenesis approaches, we investigated which subunits govern the interaction of telomerase holoenzyme with telomeres. Our results show that Teb1 is critical for telomere interaction of other holoenzyme subunits and demonstrate that high-affinity Teb1 DNA-binding activity is necessary and sufficient for cell cycle-regulated telomere association. Overall, these and additional findings indicate that in the ciliate Tetrahymena, telomerase recruitment to telomeres requires direct binding to single-stranded DNA, unlike the indirect DNA recognition through telomere-bound proteins essential in yeast and mammalian cells. (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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