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Dynamics of TRF1 organizing a single human telomere

Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic twee...

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Autores principales: Li, Xu, Wang, Meijie, Zheng, Wei, Huang, Wei, Wang, Zeyu, Jin, Kairang, Liu, Lin, Yu, Zhongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826288/
https://www.ncbi.nlm.nih.gov/pubmed/33347580
http://dx.doi.org/10.1093/nar/gkaa1222
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author Li, Xu
Wang, Meijie
Zheng, Wei
Huang, Wei
Wang, Zeyu
Jin, Kairang
Liu, Lin
Yu, Zhongbo
author_facet Li, Xu
Wang, Meijie
Zheng, Wei
Huang, Wei
Wang, Zeyu
Jin, Kairang
Liu, Lin
Yu, Zhongbo
author_sort Li, Xu
collection PubMed
description Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic tweezers, we here investigated the dynamics of TRF1 upon organizing a human telomere and the protein-DNA interactions at a moving telomeric fork. We first developed a method to obtain telomeres from human cells for directly measuring the telomere length by single-molecule force spectroscopy. Next, we examined the compaction and decompaction of a telomere by TRF1 dimers. TRF1 dissociates from a compacted telomere with heterogenous loops in ∼20 s. We also found a negative correlation between the number of telomeric loops and loop sizes. We further characterized the dynamics of TRF1 at a telomeric DNA fork. With binding energies of 11 k(B)T, TRF1 can modulate the forward and backward steps of DNA fork movements by 2–9 s at a critical force of F(1/2), temporarily maintaining the telomeric fork open. Our results shed light on the mechanisms of how TRF1 organizes human telomeres and facilitates the efficient replication of telomeric DNA. Our work will help future research on the chemical biology of telomeres and shelterin-targeted drug discovery.
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spelling pubmed-78262882021-01-27 Dynamics of TRF1 organizing a single human telomere Li, Xu Wang, Meijie Zheng, Wei Huang, Wei Wang, Zeyu Jin, Kairang Liu, Lin Yu, Zhongbo Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic tweezers, we here investigated the dynamics of TRF1 upon organizing a human telomere and the protein-DNA interactions at a moving telomeric fork. We first developed a method to obtain telomeres from human cells for directly measuring the telomere length by single-molecule force spectroscopy. Next, we examined the compaction and decompaction of a telomere by TRF1 dimers. TRF1 dissociates from a compacted telomere with heterogenous loops in ∼20 s. We also found a negative correlation between the number of telomeric loops and loop sizes. We further characterized the dynamics of TRF1 at a telomeric DNA fork. With binding energies of 11 k(B)T, TRF1 can modulate the forward and backward steps of DNA fork movements by 2–9 s at a critical force of F(1/2), temporarily maintaining the telomeric fork open. Our results shed light on the mechanisms of how TRF1 organizes human telomeres and facilitates the efficient replication of telomeric DNA. Our work will help future research on the chemical biology of telomeres and shelterin-targeted drug discovery. Oxford University Press 2020-12-21 /pmc/articles/PMC7826288/ /pubmed/33347580 http://dx.doi.org/10.1093/nar/gkaa1222 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Li, Xu
Wang, Meijie
Zheng, Wei
Huang, Wei
Wang, Zeyu
Jin, Kairang
Liu, Lin
Yu, Zhongbo
Dynamics of TRF1 organizing a single human telomere
title Dynamics of TRF1 organizing a single human telomere
title_full Dynamics of TRF1 organizing a single human telomere
title_fullStr Dynamics of TRF1 organizing a single human telomere
title_full_unstemmed Dynamics of TRF1 organizing a single human telomere
title_short Dynamics of TRF1 organizing a single human telomere
title_sort dynamics of trf1 organizing a single human telomere
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826288/
https://www.ncbi.nlm.nih.gov/pubmed/33347580
http://dx.doi.org/10.1093/nar/gkaa1222
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