NDLI: Tethering telomeric double- and single-stranded DNA-binding proteins inhibits telomere elongation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Barrientos, Katharine S. Ozgur, Sezgin Counter, Christopher M. Etheridge, Katherine T. Griffith, Jack D. Compton, Sarah A.
Description	Author Affiliation: Etheridge KT ( Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.)
Abstract	Mammalian telomeres are composed of G-rich repetitive double-stranded (ds) DNA with a 3' single-stranded (ss) overhang and associated proteins that together maintain chromosome end stability. Complete replication of telomeric DNA requires de novo elongation of the ssDNA by the enzyme telomerase, with telomeric proteins playing a key role in regulating telomerase-mediated telomere replication. In regards to the protein component of mammalian telomeres, TRF1 and TRF2 bind to the dsDNA of telomeres, whereas POT1 binds to the ssDNA portion. These three proteins are linked through either direct interactions or by the proteins TIN2 and TPP1. To determine the biological consequence of connecting telomeric dsDNA to ssDNA through a multiprotein assembly, we compared the effect of expressing TRF1 and POT1 in trans versus in cis in the form of a fusion of these two proteins, on telomere length in telomerase-positive cells. When expressed in trans these two proteins induced extensive telomere elongation. Fusing TRF1 to POT1 abrogated this effect, inducing mild telomere shortening, and generated looped DNA structures, as assessed by electron microscopy, consistent with the protein forming a complex with dsDNA and ssDNA. We speculate that such a protein bridge between dsDNA and ssDNA may inhibit telomerase access, promoting telomere shortening.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	11
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-14
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA, Single-Stranded Chemistry DNA-Binding Proteins DNA Gene Expression Regulation Nuclear Proteins Physiology Telomere-Binding Proteins Telomeric Repeat Binding Protein 1 Telomeric Repeat Binding Protein 2 Cell Line Microscopy, Fluorescence Models, Biological Nucleic Acid Conformation Protein Binding Telomerase Metabolism Telomere Ultrastructure Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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