Cited by 422Telomeres, Telomerase, and SenescenceDNA Repair MechanismsDNA and Nucleic Acid Chemistry

Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres

Open access
Wu, Ling, Multani, Asha S., He, Hua, Cosme-Blanco, Wilfredo, Deng, Yu, Deng, Jian Min, Bachilo, Olga, Pathak, Sen +5 more·2006·Cell

Abstract

The terminal t-loop structure adopted by mammalian telomeres is thought to prevent telomeres from being recognized as double-stranded DNA breaks by sequestering the 3' single-stranded G-rich overhang from exposure to the DNA damage machinery. The POT1 (protection of telomeres) protein binds the single-stranded overhang and is required for both chromosomal end protection and telomere length regulation. The mouse genome contains two POT1 orthologs, Pot1a and Pot1b. Here we show that conditional deletion of Pot1a elicits a DNA damage response at telomeres, resulting in p53-dependent replicative senescence. Pot1a-deficient cells exhibit overall telomere length and 3' overhang elongation as well as aberrant homologous recombination (HR) at telomeres, manifested as increased telomere sister chromatid exchanges and formation of telomere circles. Telomeric HR following Pot1a loss requires NBS1. Pot1a deletion also results in chromosomal instability. Our results suggest that POT1a is crucial for the maintenance of both telomere integrity and overall genomic stability.

Integrity signals

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Crossref · 10.1016/j.cell.2006.05.037

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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 [18]

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Authors
Wu, L., Multani, A. S., He, H., Cosme-Blanco, W., Deng, Y., Deng, J. M., Bachilo, O., Pathak, S., Tahara, H., Bailey, S. M., Deng, Y., Behringer, R. R., & Chang, S.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Rice University (US)
  • Hiroshima University (JP)
  • Colorado State University (US)
Corresponding author
Chang, Sandy
Venue
Cell
Publisher
Elsevier BV
Published
2006-07
Volume
126
Issue
1
Pages
49-62
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2147765162
Cited by
422
References
64
Citations by year
2026: 6 · 2025: 11 · 2024: 7 · 2023: 10 · 2022: 11 · 2021: 20 · 2020: 15 · 2019: 15 · 2018: 12 · 2017: 17 · 2016: 18 · 2015: 20 · 2014: 20 · 2013: 24 · 2012: 30
FWCI
25.03
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA 016672, R01CA129037, P30CA016672)
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, telomeres, DNA damage checkpoint, homologous recombination, T-loop, 3' overhangs, DNA damage response, p53, replicative senescence, NBS1, sister chromatid exchange, chromosomal instability, genome stability, telomere length regulation
MeSH terms
Shelterin Complex, Animals, Cells, Cultured, Chromosome Aberrations, DNA Damage, DNA Repair, DNA-Binding Proteins, Nuclear Proteins, Recombination, Genetic, Sister Chromatid Exchange, Telomere, Cellular Senescence, Sequence Homology, Mice, Knockout, Cell Cycle Proteins, Genes, cdc, Protein Isoforms, Gene Silencing, Telomere-Binding Proteins, Genomic Instability, Mice

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