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TRF1 and TRF2 use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres

Lin, Jiangguo, Countryman, Preston, Buncher, Noah, Kaur, Parminder, Longjiang, E., Zhang, Yiyun, Gibson, Greg, You, Changjiang, Watkins, Simon C, Piehler, Jacob, and others. (2014) TRF1 and TRF2 use different mechanisms to find telomeric DNA but share a novel mechanism to search for protein partners at telomeres. Nucleic acids research, 42 (4). pp. 2493-2504. ISSN 1362-4962. (doi:10.1093/nar/gkt1132) (KAR id:42940)

Abstract

Human telomeres are maintained by the shelterin protein complex in which TRF1 and TRF2 bind directly to duplex telomeric DNA. How these proteins find telomeric sequences among a genome of billions of base pairs and how they find protein partners to form the shelterin complex remains uncertain. Using single-molecule fluorescence imaging of quantum dot-labeled TRF1 and TRF2, we study how these proteins locate TTAGGG repeats on DNA tightropes. By virtue of its basic domain TRF2 performs an extensive 1D search on nontelomeric DNA, whereas TRF1's 1D search is limited. Unlike the stable and static associations observed for other proteins at specific binding sites, TRF proteins possess reduced binding stability marked by transient binding (? 9-17 s) and slow 1D diffusion on specific telomeric regions. These slow diffusion constants yield activation energy barriers to sliding ? 2.8-3.6 ?(B)T greater than those for nontelomeric DNA. We propose that the TRF proteins use 1D sliding to find protein partners and assemble the shelterin complex, which in turn stabilizes the interaction with specific telomeric DNA. This 'tag-team proofreading' represents a more general mechanism to ensure a specific set of proteins interact with each other on long repetitive specific DNA sequences without requiring external energy sources.

Item Type: Article
DOI/Identification number: 10.1093/nar/gkt1132
Additional information: Open Access
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Neil Kad
Date Deposited: 15 Sep 2014 19:14 UTC
Last Modified: 28 Jan 2021 09:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/42940 (The current URI for this page, for reference purposes)

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