Cited by 203Telomeres, Telomerase, and SenescenceDNA Repair MechanismsDNA and Nucleic Acid Chemistry

Molecular mechanisms of activity and derepression of alternative lengthening of telomeres

Pickett, Hilda A, Reddel, Roger R·2015·Nature Structural & Molecular Biology

Abstract

Alternative lengthening of telomeres (ALT) involves homology-directed telomere synthesis. This multistep process is facilitated by loss of the ATRX or DAXX chromatin-remodeling factors and by abnormalities of the telomere nucleoprotein architecture, including altered DNA sequence and decreased TRF2 saturation. Induction of telomere-specific DNA damage triggers homology-directed searches, and NuRD-ZNF827 protein-protein interactions provide a platform for the telomeric recruitment of homologous recombination (HR) proteins. Telomere lengthening proceeds by strand exchange and template-driven DNA synthesis, which culminates in dissolution of HR intermediates.

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Crossref · 10.1038/nsmb.3106

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  • A significant minority of cancers use alternative lengthening of telomeres (ALT) to maintain telomeres.

    “Furthermore, although most human cancers (~90%) escape telomere crisis by activating telomerase56, a significant minority of cancers use an alternative telomere maintenance system, referred to as alternative lengthening of telomeres (ALT)161.”

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Authors
Pickett, H. A., & Reddel, R. R.
Affiliations
The University of Sydney (AU)
Corresponding author
  • Pickett, Hilda A
  • Reddel, Roger R
Venue
Nature Structural & Molecular Biology
Published
2015-11
Volume
22
Issue
11
Pages
875-880
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2193590034
Cited by
203
References
81
Citations by year
2026: 14 · 2025: 10 · 2024: 12 · 2023: 10 · 2022: 13 · 2021: 22 · 2020: 27 · 2019: 24 · 2018: 20 · 2017: 28 · 2016: 20 · 2015: 2 · 2014: 1
FWCI
2.85
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
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
alternative lengthening of telomeres, telomere maintenance, homology-directed recombination, telomere synthesis, ATRX, DAXX, chromatin remodeling, TRF2, NuRD complex, strand exchange, telomere shortening, cancer cells
MeSH terms
DNA Helicases, Nuclear Proteins, Telomere, Telomere Homeostasis, Homologous Recombination

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