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Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins.
J Cell Biol. 2009 Jun 01; 185(5):797-810.JC

Abstract

Alternative lengthening of telomeres (ALT) is a recombination-mediated process that maintains telomeres in telomerase-negative cancer cells. In asynchronously dividing ALT-positive cell populations, a small fraction of the cells have ALT-associated promyelocytic leukemia nuclear bodies (APBs), which contain (TTAGGG)n DNA and telomere-binding proteins. We found that restoring p53 function in ALT cells caused p21 up-regulation, growth arrest/senescence, and a large increase in cells containing APBs. Knockdown of p21 significantly reduced p53-mediated induction of APBs. Moreover, we found that heterochromatin protein 1 (HP1) is present in APBs, and knockdown of HP1alpha and/or HP1gamma prevented p53-mediated APB induction, which suggests that HP1-mediated chromatin compaction is required for APB formation. Therefore, although the presence of APBs in a cell line or tumor is an excellent qualitative marker for ALT, the association of APBs with growth arrest/senescence and with "closed" telomeric chromatin, which is likely to repress recombination, suggests there is no simple correlation between ALT activity level and the number of APBs or APB-positive cells.

Authors+Show Affiliations

Cancer Research Unit, Children's Medical Research Institute, Westmead 2145, New South Wales, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19468068

Citation

Jiang, Wei-Qin, et al. "Induction of Alternative Lengthening of Telomeres-associated PML Bodies By P53/p21 Requires HP1 Proteins." The Journal of Cell Biology, vol. 185, no. 5, 2009, pp. 797-810.
Jiang WQ, Zhong ZH, Nguyen A, et al. Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins. J Cell Biol. 2009;185(5):797-810.
Jiang, W. Q., Zhong, Z. H., Nguyen, A., Henson, J. D., Toouli, C. D., Braithwaite, A. W., & Reddel, R. R. (2009). Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins. The Journal of Cell Biology, 185(5), 797-810. https://doi.org/10.1083/jcb.200810084
Jiang WQ, et al. Induction of Alternative Lengthening of Telomeres-associated PML Bodies By P53/p21 Requires HP1 Proteins. J Cell Biol. 2009 Jun 1;185(5):797-810. PubMed PMID: 19468068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of alternative lengthening of telomeres-associated PML bodies by p53/p21 requires HP1 proteins. AU - Jiang,Wei-Qin, AU - Zhong,Ze-Huai, AU - Nguyen,Akira, AU - Henson,Jeremy D, AU - Toouli,Christian D, AU - Braithwaite,Antony W, AU - Reddel,Roger R, Y1 - 2009/05/25/ PY - 2009/5/27/entrez PY - 2009/5/27/pubmed PY - 2009/7/14/medline SP - 797 EP - 810 JF - The Journal of cell biology JO - J. Cell Biol. VL - 185 IS - 5 N2 - Alternative lengthening of telomeres (ALT) is a recombination-mediated process that maintains telomeres in telomerase-negative cancer cells. In asynchronously dividing ALT-positive cell populations, a small fraction of the cells have ALT-associated promyelocytic leukemia nuclear bodies (APBs), which contain (TTAGGG)n DNA and telomere-binding proteins. We found that restoring p53 function in ALT cells caused p21 up-regulation, growth arrest/senescence, and a large increase in cells containing APBs. Knockdown of p21 significantly reduced p53-mediated induction of APBs. Moreover, we found that heterochromatin protein 1 (HP1) is present in APBs, and knockdown of HP1alpha and/or HP1gamma prevented p53-mediated APB induction, which suggests that HP1-mediated chromatin compaction is required for APB formation. Therefore, although the presence of APBs in a cell line or tumor is an excellent qualitative marker for ALT, the association of APBs with growth arrest/senescence and with "closed" telomeric chromatin, which is likely to repress recombination, suggests there is no simple correlation between ALT activity level and the number of APBs or APB-positive cells. SN - 1540-8140 UR - https://www.unboundmedicine.com/medline/citation/19468068/Induction_of_alternative_lengthening_of_telomeres_associated_PML_bodies_by_p53/p21_requires_HP1_proteins_ L2 - https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.200810084 DB - PRIME DP - Unbound Medicine ER -