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De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation.
J Cell Sci. 2011 Nov 01; 124(Pt 21):3603-18.JC

Abstract

Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway.

Authors+Show Affiliations

German Cancer Research Center & BioQuant, Research Group Genome Organization & Function, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22045732

Citation

Chung, Inn, et al. "De Novo Assembly of a PML Nuclear Subcompartment Occurs Through Multiple Pathways and Induces Telomere Elongation." Journal of Cell Science, vol. 124, no. Pt 21, 2011, pp. 3603-18.
Chung I, Leonhardt H, Rippe K. De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. J Cell Sci. 2011;124(Pt 21):3603-18.
Chung, I., Leonhardt, H., & Rippe, K. (2011). De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. Journal of Cell Science, 124(Pt 21), 3603-18. https://doi.org/10.1242/jcs.084681
Chung I, Leonhardt H, Rippe K. De Novo Assembly of a PML Nuclear Subcompartment Occurs Through Multiple Pathways and Induces Telomere Elongation. J Cell Sci. 2011 Nov 1;124(Pt 21):3603-18. PubMed PMID: 22045732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. AU - Chung,Inn, AU - Leonhardt,Heinrich, AU - Rippe,Karsten, Y1 - 2011/11/01/ PY - 2011/11/3/entrez PY - 2011/11/3/pubmed PY - 2012/3/27/medline SP - 3603 EP - 18 JF - Journal of cell science JO - J. Cell. Sci. VL - 124 IS - Pt 21 N2 - Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway. SN - 1477-9137 UR - https://www.unboundmedicine.com/medline/citation/22045732/De_novo_assembly_of_a_PML_nuclear_subcompartment_occurs_through_multiple_pathways_and_induces_telomere_elongation_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=22045732 DB - PRIME DP - Unbound Medicine ER -