Dynamics of TRF1 organizing a single human telomere
| Autor: | Wang Zeyu, Kairang Jin, Lin Liu, Zhongbo Yu, Wei Zheng, Li Xu, Meijie Wang, Huang Wei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Magnetic tweezers
AcademicSubjects/SCI00010 Telomere-Binding Proteins Chemical biology Biology Shelterin Complex Telomere organization 03 medical and health sciences chemistry.chemical_compound Micromanipulation 0302 clinical medicine Genetics Humans Biotinylation Telomeric Repeat Binding Protein 1 030304 developmental biology 0303 health sciences Drug discovery Gene regulation Chromatin and Epigenetics Inverted Repeat Sequences Force spectroscopy Telomere Shelterin Single Molecule Imaging Cell biology chemistry Magnets K562 Cells Digoxigenin 030217 neurology & neurosurgery DNA |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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 kBT, TRF1 can modulate the forward and backward steps of DNA fork movements by 2–9 s at a critical force of F1/2, 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. Graphical Abstract Graphical AbstractWe use single-molecule magnetic tweezers to precisely measure the absolute length of single human telomeres and reveal the dynamics of TRF1 upon organizing a telomere. |
| Databáze: | OpenAIRE |
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