Recent Expansion of the Telomeric Complex in Rodents: Two Distinct POT1 Proteins Protect Mouse Telomeres
Open accessAbstract
Human telomeres are protected by shelterin, a complex that includes the POT1 single-stranded DNA binding protein. We found that mouse telomeres contain two POT1 paralogs, POT1a and POT1b, and we used conditional deletion to determine their function. Double-knockout cells showed that POT1a/b are required to prevent a DNA damage signal at chromosome ends, endoreduplication, and senescence. In contrast, POT1a/b were largely dispensable for repression of telomere fusions. Single knockouts and complementation experiments revealed that POT1a and POT1b have distinct functions. POT1a, but not POT1b, was required to repress a DNA damage signal at telomeres. Conversely, POT1b, but not POT1a, had the ability to regulate the amount of single-stranded DNA at the telomere terminus. We conclude that mouse telomeres require two distinct POT1 proteins whereas human telomeres have one. Such divergence is unprecedented in mammalian chromosome biology and has implications for modeling human telomere biology in mice.
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Loss of POT1 impairs telomere capping, showing that POT1 and TPP1 protect the single-stranded portion of telomeres.
“POT1 and TPP1 serve a role in protecting the single-stranded portion of the telomere because loss of POT1 impairs telomere capping (16)(17)(18)(19).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [17]
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- Authors
- Hockemeyer, D., Daniels, J.-P., Takai, H., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 126
- Issue
- 1
- Pages
- 63-77
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2058375396
- Cited by
- 397
- References
- 13
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 16 · 2020: 16 · 2019: 15 · 2018: 13 · 2017: 21 · 2016: 16 · 2015: 21 · 2014: 22 · 2013: 23 · 2012: 30
- FWCI
- 22.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2604 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- National Institute on Aging (AG16642)
- National Institute of General Medical Sciences (GM 49046)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- telomeres, POT1, shelterin, endoreduplication, cellular senescence, telomere fusion, single-stranded DNA, paralogs, conditional knockout
- MeSH terms
- Shelterin Complex, Animals, Cell Division, Cells, Cultured, DNA Damage, DNA Replication, DNA-Binding Proteins, DNA, Single-Stranded, Genes, Lethal, Humans, Repressor Proteins, Species Specificity, Signal Transduction, Telomere, Cellular Senescence, Mice, Knockout, Evolution, Molecular, Protein Isoforms, Telomere-Binding Proteins, Telomeric Repeat Binding Protein 2, Genomic Instability, Cell Proliferation, Mice
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