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ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle.
J Cell Sci 2000; 113 Pt 24:4577-85JC

Abstract

Telomere maintenance is essential for the unlimited proliferative potential of human cells, and hence immortalization. However, a number of tumors, tumor-derived cell lines and in vitro immortalized cell lines have been described that do not express detectable telomerase activity. These lines utilize a mechanism, termed Alternative Lengthening of Telomeres (ALT), to provide telomere maintenance. A subset of the cells in each ALT cell line contain a novel form of the promyelocytic leukemia nuclear body (PML NB) in which telomeric DNA and the telomere binding proteins TRF1 and TRF2 co-localize with the PML protein, termed ALT-associated PML bodies (AA-PBs). In contrast, in non-ALT, telomerase-positive cell lines these telomeric proteins and the PML NB occupy distinct and separate subnuclear domains. PML NBs have been implicated in terminal differentiation, growth suppression and apoptosis. The role, if any, of AA-PBs in telomere maintenance or culture viability in telomerase negative cell lines is unclear, but it has been suggested that cells containing these structures are no longer viable and are marked for eventual death. We utilized a series of human ovarian surface epithelium (HOSE) cell lines that use ALT for telomere maintenance to determine if AA-PBs are indeed markers of cells in these cultures that are no longer cycling. We show that AA-PB positive cells incorporate BrdU and thus are able to carry out DNA replication. In addition, AA-PBs are present in mitotic cells and the frequency of cells containing these structures is increased when cultures are enriched for cells in the G(2)/M phase of the cell cycle suggesting that the formation of AA-PBs is coordinately regulated with the cell cycle. Finally, we demonstrate that the majority of the AA-PB positive cells in the culture are not destined for immediate apoptosis. Taken together the data argue against AA-PBs marking cells destined for death and, instead, raise the possibility that these structures may be actively involved in telomere maintenance via the ALT pathway.

Authors+Show Affiliations

Fox Chase Cancer Center, Philadelphia PA 1911, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11082050

Citation

Grobelny, J V., et al. "ALT-associated PML Bodies Are Present in Viable Cells and Are Enriched in Cells in the G(2)/M Phase of the Cell Cycle." Journal of Cell Science, vol. 113 Pt 24, 2000, pp. 4577-85.
Grobelny JV, Godwin AK, Broccoli D. ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle. J Cell Sci. 2000;113 Pt 24:4577-85.
Grobelny, J. V., Godwin, A. K., & Broccoli, D. (2000). ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle. Journal of Cell Science, 113 Pt 24, pp. 4577-85.
Grobelny JV, Godwin AK, Broccoli D. ALT-associated PML Bodies Are Present in Viable Cells and Are Enriched in Cells in the G(2)/M Phase of the Cell Cycle. J Cell Sci. 2000;113 Pt 24:4577-85. PubMed PMID: 11082050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ALT-associated PML bodies are present in viable cells and are enriched in cells in the G(2)/M phase of the cell cycle. AU - Grobelny,J V, AU - Godwin,A K, AU - Broccoli,D, PY - 2000/11/18/pubmed PY - 2001/3/27/medline PY - 2000/11/18/entrez SP - 4577 EP - 85 JF - Journal of cell science JO - J. Cell. Sci. VL - 113 Pt 24 N2 - Telomere maintenance is essential for the unlimited proliferative potential of human cells, and hence immortalization. However, a number of tumors, tumor-derived cell lines and in vitro immortalized cell lines have been described that do not express detectable telomerase activity. These lines utilize a mechanism, termed Alternative Lengthening of Telomeres (ALT), to provide telomere maintenance. A subset of the cells in each ALT cell line contain a novel form of the promyelocytic leukemia nuclear body (PML NB) in which telomeric DNA and the telomere binding proteins TRF1 and TRF2 co-localize with the PML protein, termed ALT-associated PML bodies (AA-PBs). In contrast, in non-ALT, telomerase-positive cell lines these telomeric proteins and the PML NB occupy distinct and separate subnuclear domains. PML NBs have been implicated in terminal differentiation, growth suppression and apoptosis. The role, if any, of AA-PBs in telomere maintenance or culture viability in telomerase negative cell lines is unclear, but it has been suggested that cells containing these structures are no longer viable and are marked for eventual death. We utilized a series of human ovarian surface epithelium (HOSE) cell lines that use ALT for telomere maintenance to determine if AA-PBs are indeed markers of cells in these cultures that are no longer cycling. We show that AA-PB positive cells incorporate BrdU and thus are able to carry out DNA replication. In addition, AA-PBs are present in mitotic cells and the frequency of cells containing these structures is increased when cultures are enriched for cells in the G(2)/M phase of the cell cycle suggesting that the formation of AA-PBs is coordinately regulated with the cell cycle. Finally, we demonstrate that the majority of the AA-PB positive cells in the culture are not destined for immediate apoptosis. Taken together the data argue against AA-PBs marking cells destined for death and, instead, raise the possibility that these structures may be actively involved in telomere maintenance via the ALT pathway. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/11082050/ALT_associated_PML_bodies_are_present_in_viable_cells_and_are_enriched_in_cells_in_the_G_2_/M_phase_of_the_cell_cycle_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11082050 DB - PRIME DP - Unbound Medicine ER -