Human shelterin protein POT1 prevents severe telomere instability induced by homology‐directed DNA repair
Open accessPublished version of a preprint
Abstract
The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through genetics and proteomics, discovering that a complete absence of POT1 leads to severe telomere maintenance defects that had not been anticipated from previous depletion studies in human cells. Conditional deletion of POT1 in HEK293E cells gives rise to rapid telomere elongation and length heterogeneity, branched telomeric DNA structures, telomeric R-loops, and telomere fragility. We determine the telomeric proteome upon POT1-loss, implementing an improved telomeric chromatin isolation protocol. We identify a large set of proteins involved in nucleic acid metabolism that engage with telomeres upon POT1-loss. Inactivation of the homology-directed repair machinery suppresses POT1-loss-mediated telomeric DNA defects. Our results unravel as major function of human POT1 the suppression of telomere instability induced by homology-directed repair.
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Kulak, N. A., Pichler, G., Paron, I., Nagaraj, N., & Mann, M. (2014) · Nature Methods · doi:10.1038/nmeth.2834 · Cited by 1,719 · see citing works
Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication
Sfeir, A., Kosiyatrakul, S. T., Hockemeyer, D., MacRae, S. L., Karlseder, J., Schildkraut, C. L., & de Lange, T. (2009) · Cell · doi:10.1016/j.cell.2009.06.021 · Cited by 990 · see citing works
Super-Resolution Fluorescence Imaging of Telomeres Reveals TRF2-Dependent T-loop Formation
Doksani, Y., Wu, J. Y., de Lange, T., & Zhuang, X. (2013) · Cell · doi:10.1016/j.cell.2013.09.048 · Cited by 493 · cited 1× · see citing works
“Alternatively, when telomeres adopt a t-loop structure in which the single-stranded 3 0 overhang is tucked into double-stranded part of the telomere (Doksani et al , 2013), POT1 is thought to bind to the single-stranded displaced G-rich strand.”
Wu, L., Multani, A. S., He, H., Cosme-Blanco, W., Deng, Y., Deng, J. M., Bachilo, O., Pathak, S., Tahara, H., Bailey, S. M., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.037 · Cited by 422 · see citing works
Hockemeyer, D., Sfeir, A. J., Shay, J. W., Wright, W. E., & de Lange, T. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600733 · Cited by 314 · see citing works
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- Authors
- Glousker, G., Briod, A., Quadroni, M., & Lingner, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- University of Lausanne (CH)
- Corresponding author
- Lingner, Joachim
- Venue
- The EMBO Journal
- Published
- 2020-10-19
- Volume
- 39
- Issue
- 23
- Pages
- e104500-e104500
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC7705456
- OpenAlex
- W3093230859
- Cited by
- 51
- References
- 6
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 1
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Swiss National Science Foundation (310030_184718)
- Swiss Cancer League (KLS‐3824-02‐2016)
- NCCR RNA & disease network of the SNSF (182880)
- Initial Training Network (ITN) grant (aDDRess) from the European Commission's Seventh Framework Programme (812829)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- POT1, shelterin, telomere maintenance, telomere instability, homology-directed repair, telomeric DNA, telomere fragility, conditional gene deletion, DNA damage checkpoint, nucleic acid metabolism
- MeSH terms
- Shelterin Complex, Cell Cycle, DNA, DNA, Single-Stranded, HeLa Cells, Humans, Phenotype, Telomere, Proteome, Telomere-Binding Proteins, Gene Knockout Techniques, HEK293 Cells, Transcriptome, Recombinational DNA Repair
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