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Probing PML body function in ALT cells reveals spatiotemporal requirements for telomere recombination.
Open accessAbstract
Promyelocytic leukemia (PML) bodies (also called ND10) are dynamic nuclear structures implicated in a wide variety of cellular processes. ALT-associated PML bodies (APBs) are specialized PML bodies found exclusively in telomerase-negative tumors in which telomeres are maintained by recombination-based alternative (ALT) mechanisms. Although it has been suggested that APBs are directly implicated in telomere metabolism of ALT cells, their precise role and structure have remained elusive. Here we show that PML bodies in ALT cells associate with chromosome ends forming small, spatially well-defined clusters, containing on average 2–5 telomeres. Using an innovative approach that gently enlarges PML bodies in living cells while retaining their overall organization, we show that this physical enlargement of APBs spatially resolves the single telomeres in the cluster, but does not perturb the potential of the APB to recruit chromosome extremities. We show that telomere clustering in PML bodies is cell-cycle regulated and that unique telomeres within a cluster associate with recombination proteins. Enlargement of APBs induced the accumulation of telomere-telomere recombination intermediates visible on metaphase spreads and connecting heterologous chromosomes. The strand composition of these recombination intermediates indicated that this recombination is constrained to a narrow time window in the cell cycle following replication. These data provide strong evidence that PML bodies are not only a marker for ALT cells but play a direct role in telomere recombination, both by bringing together chromosome ends and by promoting telomere-telomere interactions between heterologous chromosomes.
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“These ALT-associated PML bodies have an essential role in telomere-lengthening in ALT+ cells, by bringing chromosome ends together with the recombination proteins that mediate their lengthening (Draskovic et al., 2009; Osterwald et al., 2015).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Draskovic et al., 2009
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Metadata
- Authors
- Draskovic, I., Arnoult, N., Steiner, V., Bacchetti, S., Lomonte, P., & Londoño-Vallejo, A.
- Affiliations
- Institut Curie, 26 rue d'Ulm, 75248 Paris, France; Université Pierre et Marie Curie 06, 75005 Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3244;
- Centre National de la Recherche Scientifique (FR)
- Instituto Nazionale Tumori Regina Elena (IT)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-09-15
- Volume
- 106
- Issue
- 37
- Pages
- 15726-15731
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2747187
- OpenAlex
- W2075977300
- Cited by
- 175
- References
- 34
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 15 · 2023: 15 · 2022: 11 · 2021: 18 · 2020: 13 · 2019: 12 · 2018: 2 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 10 · 2012: 13
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PML bodies, ALT-associated PML bodies, telomere recombination, alternative lengthening of telomeres, telomere clustering, telomerase-negative cells, cell cycle regulation, recombination intermediates, ND10
- MeSH terms
- Promyelocytic Leukemia Protein, Cell Cycle, Cell Line, Humans, Nuclear Proteins, Recombination, Genetic, Transcription Factors, Telomere, In Situ Hybridization, Fluorescence, Fluorescent Antibody Technique, Indirect, Telomerase, Tumor Suppressor Proteins, Telomeric Repeat Binding Protein 2, Intranuclear Space, Cell Line, Tumor
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