The POT1-TPP1 telomere complex is a telomerase processivity factor.
Open accessAbstract
Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.
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TPP1 interacts directly with telomerase and is a processivity factor for telomerase-mediated telomere lengthening.
“In addition, TPP1 interacts directly with telomerase and is a processivity factor for telomerase-mediated telomere lengthening (Wang et al., 2007; Xu et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Wang et al., 2007
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- Authors
- Wang, F., Podell, E. R., Zaug, A. J., Yang, Y., Baciu, P., Cech, T. R., & Lei, M.
- Affiliations
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lei, Ming
- Venue
- Nature
- Published
- 2007-01-21
- Volume
- 445
- Issue
- 7127
- Pages
- 506-510
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2011882274
- Cited by
- 704
- References
- 38
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 34 · 2023: 32 · 2022: 26 · 2021: 40 · 2020: 31 · 2019: 32 · 2018: 32 · 2017: 31 · 2016: 28 · 2015: 38 · 2014: 49 · 2013: 40 · 2012: 38
- FWCI
- 40.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- POT1, TPP1, telomerase, telomerase processivity, shelterin complex, telomeres, telomere elongation, telomere protection
- MeSH terms
- Shelterin Complex, DNA, Single-Stranded, Humans, Nucleic Acid Conformation, Protein Binding, Protein Structure, Tertiary, Crystallography, X-Ray, Telomerase, Protein Subunits, Telomere-Binding Proteins, Structural Homology, Protein, Multiprotein Complexes
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