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[Cancer Research 59, 4175-4179, September 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 4175-4179, September 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Telomerase-negative Immortalized Human Cells Contain a Novel Type of Promyelocytic Leukemia (PML) Body1

Thomas R. Yeager, Axel A. Neumann, Anna Englezou, Lily I. Huschtscha, Jane R. Noble and Roger R. Reddel2

Children’s Medical Research Institute, Westmead, Sydney, New South Wales 2145, Australia

Telomerase-negative immortalized human cells maintain their telomeres by a mechanism known as alternative lengthening of telomeres (ALT). We report here that ALT cells contain a novel promyelocytic leukemia (PML) body (ALT-associated PML body, APB). APBs are large donut-shaped nuclear structures containing PML protein, telomeric DNA, and the telomere binding proteins human telomere repeat binding factors 1 and 2. Immunostaining showed that APBs also contain replication factor A, RAD51, and RAD52, proteins involved in DNA synthesis and recombination. During immortalization, APBs appeared at exactly the same time as activation of ALT. APBs were found in ALT tumors and cell lines but not in mortal cell strains or in telomerase-positive cell lines or tumors.




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R. N. Damle, F. M. Batliwalla, F. Ghiotto, A. Valetto, E. Albesiano, C. Sison, S. L. Allen, J. Kolitz, V. P. Vinciguerra, P. Kudalkar, et al.
Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations
Blood, January 15, 2004; 103(2): 375 - 382.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
Y. Zhu, R. L. Tomlinson, A. A. Lukowiak, R. M. Terns, and M. P. Terns
Telomerase RNA Accumulates in Cajal Bodies in Human Cancer Cells
Mol. Biol. Cell, January 1, 2004; 15(1): 81 - 90.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. Velicescu, J. Yu, B.-S. Herbert, J. W. Shay, E. Granada, and L. Dubeau
Aneuploidy and Telomere Attrition Are Independent Determinants of Crisis in SV40-transformed Epithelial Cells
Cancer Res., September 15, 2003; 63(18): 5813 - 5820.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
Z.-X. Xu, A. Timanova-Atanasova, R.-X. Zhao, and K.-S. Chang
PML Colocalizes with and Stabilizes the DNA Damage Response Protein TopBP1
Mol. Cell. Biol., June 15, 2003; 23(12): 4247 - 4256.
[Abstract] [Full Text] [PDF]

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 BloodHome page
K.-D. Wu, L. M. Orme, J. Shaughnessy Jr, J. Jacobson, B. Barlogie, and M. A. S. Moore
Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival
Blood, June 15, 2003; 101(12): 4982 - 4989.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
G. Wu, X. Jiang, W.-H. Lee, and P.-L. Chen
Assembly of Functional ALT-associated Promyelocytic Leukemia Bodies Requires Nijmegen Breakage Syndrome 1
Cancer Res., May 15, 2003; 63(10): 2589 - 2595.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
P. L. Opresko, W.-H. Cheng, C. von Kobbe, J. A. Harrigan, and V. A. Bohr
Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process.
Carcinogenesis, May 1, 2003; 24(5): 791 - 802.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
T. Tsutsui, S.-i. Kumakura, Y. Tamura, T. W. Tsutsui, M. Sekiguchi, T. Higuchi, and J.C. Barrett
Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities
Carcinogenesis, May 1, 2003; 24(5): 953 - 965.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
S. Chang, C. M. Khoo, M. L. Naylor, R. S. Maser, and R. A. DePinho
Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression
Genes & Dev., January 1, 2003; 17(1): 88 - 100.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
D. J. Stavropoulos, P. S. Bradshaw, X. Li, I. Pasic, K. Truong, M. Ikura, M. Ungrin, and M. S. Meyn
The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis
Hum. Mol. Genet., December 1, 2002; 11(25): 3135 - 3144.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
L. Melnikova and P. Georgiev
Enhancer of terminal gene conversion, a New Mutation in Drosophila melanogaster That Induces Telomere Elongation by Gene Conversion
Genetics, November 1, 2002; 162(3): 1301 - 1312.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
P. L. Opresko, C. von Kobbe, J.-P. Laine, J. Harrigan, I. D. Hickson, and V. A. Bohr
Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases
J. Biol. Chem., October 18, 2002; 277(43): 41110 - 41119.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
W. J. Hendry III, D. M. Sheehan, S. A. Khan, and J. V. May
Developing a Laboratory Animal Model for Perinatal Endocrine Disruption: The Hamster Chronicles
Experimental Biology and Medicine, October 1, 2002; 227(9): 709 - 723.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Chang and R. A. DePinho
Telomerase extracurricular activities
PNAS, October 1, 2002; 99(20): 12520 - 12522.
[Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. A. Stewart, W. C. Hahn, B. F. O'Connor, E. N. Banner, A. S. Lundberg, P. Modha, H. Mizuno, M. W. Brooks, M. Fleming, D. B. Zimonjic, et al.
Telomerase contributes to tumorigenesis by a telomere length-independent mechanism
PNAS, October 1, 2002; 99(20): 12606 - 12611.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
K. L. B. Borden
Pondering the Promyelocytic Leukemia Protein (PML) Puzzle: Possible Functions for PML Nuclear Bodies
Mol. Cell. Biol., August 1, 2002; 22(15): 5259 - 5269.
[Full Text] [PDF]

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 Cancer Res.Home page
R. Wadhwa, L. Colgin, T. Yaguchi, K. Taira, R. R. Reddel, and S. C. Kaul
Rhodacyanine Dye MKT-077 Inhibits in Vitro Telomerase Assay But Has No Detectable Effects on Telomerase Activity in Vivo
Cancer Res., August 1, 2002; 62(15): 4434 - 4438.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. von Kobbe, P. Karmakar, L. Dawut, P. Opresko, X. Zeng, R. M. Brosh Jr., I. D. Hickson, and V. A. Bohr
Colocalization, Physical, and Functional Interaction between Werner and Bloom Syndrome Proteins
J. Biol. Chem., June 7, 2002; 277(24): 22035 - 22044.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
G. M. Siriaco, G. Cenci, A. Haoudi, L. E. Champion, C. Zhou, M. Gatti, and J. M. Mason
Telomere elongation (Tel), a New Mutation in Drosophila melanogaster That Produces Long Telomeres
Genetics, January 1, 2002; 160(1): 235 - 245.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
M. Milyavsky, A. Mimran, S. Senderovich, I. Zurer, N. Erez, I. Shats, N. Goldfinger, I. Cohen, and V. Rotter
Activation of p53 protein by telomeric (TTAGGG)n repeats
Nucleic Acids Res., December 15, 2001; 29(24): 5207 - 5215.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
M. A. Cerone, J. A. Londono-Vallejo, and S. Bacchetti
Telomere maintenance by telomerase and by recombination can coexist in human cells
Hum. Mol. Genet., September 1, 2001; 10(18): 1945 - 1952.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
J. V. Grobelny, M. Kulp-McEliece, and D. Broccoli
Effects of reconstitution of telomerase activity on telomere maintenance by the alternative lengthening of telomeres (ALT) pathway
Hum. Mol. Genet., September 1, 2001; 10(18): 1953 - 1961.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
K. Perrem, L. M. Colgin, A. A. Neumann, T. R. Yeager, and R. R. Reddel
Coexistence of Alternative Lengthening of Telomeres and Telomerase in hTERT-Transfected GM847 Cells
Mol. Cell. Biol., June 15, 2001; 21(12): 3862 - 3875.
[Abstract] [Full Text]

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 Hum Mol GenetHome page
P. Hu, S. Beresten, A. van Brabant, T.-Z. Ye, P.-P. Pandolfi, F. B. Johnson, L. Guarente, and N. A. Ellis
Evidence for BLM and Topoisomerase III{{alpha}} interaction in genomic stability
Hum. Mol. Genet., June 1, 2001; 10(12): 1287 - 1298.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
J. Burkham, D. M. Coen, C. B. C. Hwang, and S. K. Weller
Interactions of Herpes Simplex Virus Type 1 with ND10 and Recruitment of PML to Replication Compartments
J. Virol., March 1, 2001; 75(5): 2353 - 2367.
[Abstract] [Full Text]

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 Nucleic Acids ResHome page
I. Ohsugi, Y. Tokutake, N. Suzuki, T. Ide, M. Sugimoto, and Y. Furuichi
Telomere repeat DNA forms a large non-covalent complex with unique cohesive properties which is dissociated by Werner syndrome DNA helicase in the presence of replication protein A
Nucleic Acids Res., September 15, 2000; 28(18): 3642 - 3648.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. B. Lombard and L. Guarente
Nijmegen Breakage Syndrome Disease Protein and MRE11 at PML Nuclear Bodies and Meiotic Telomeres
Cancer Res., May 1, 2000; 60(9): 2331 - 2334.
[Abstract] [Full Text]

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 CarcinogenesisHome page
R. R. Reddel
The role of senescence and immortalization in carcinogenesis
Carcinogenesis, March 1, 2000; 21(3): 477 - 484.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
F. B. Johnson, D. B. Lombard, N. F. Neff, M.-A. Mastrangelo, W. Dewolf, N. A. Ellis, R. A. Marciniak, Y. Yin, R. Jaenisch, and L. Guarente
Association of the Bloom Syndrome Protein with Topoisomerase III{{alpha}} in Somatic and Meiotic Cells
Cancer Res., March 1, 2000; 60(5): 1162 - 1167.
[Abstract] [Full Text]

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 J. Cell Sci.Home page
J. Grobelny, A. Godwin, and D Broccoli
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., January 12, 2000; 113(24): 4577 - 4585.
[Abstract] [PDF]

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 J. Biol. Chem.Home page
G. Wu, W.-H. Lee, and P.-L. Chen
NBS1 and TRF1 Colocalize at Promyelocytic Leukemia Bodies during Late S/G2 Phases in Immortalized Telomerase-negative Cells. IMPLICATION OF NBS1 IN ALTERNATIVE LENGTHENING OF TELOMERES
J. Biol. Chem., September 22, 2000; 275(39): 30618 - 30622.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. P. Ford, Y. Zou, K. Pongracz, S. M. Gryaznov, J. W. Shay, and W. E. Wright
Telomerase Can Inhibit the Recombination-based Pathway of Telomere Maintenance in Human Cells
J. Biol. Chem., August 17, 2001; 276(34): 32198 - 32203.
[Abstract] [Full Text] [PDF]


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