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Alternative lengthening of telomeres in mammalian cells.
Oncogene. 2002 Jan 21; 21(4):598-610.O

Abstract

Some immortalized mammalian cell lines and tumors maintain or increase the overall length of their telomeres in the absence of telomerase activity by one or more mechanisms referred to as alternative lengthening of telomeres (ALT). Characteristics of human ALT cells include great heterogeneity of telomere size (ranging from undetectable to abnormally long) within individual cells, and ALT-associated PML bodies (APBs) that contain extrachromosomal telomeric DNA, telomere-specific binding proteins, and proteins involved in DNA recombination and replication. Activation of ALT during immortalization involves recessive mutations in genes that are as yet unidentified. Repressors of ALT activity are present in normal cells and some telomerase-positive cells. Telomere length dynamics in ALT cells suggest a recombinational mechanism. Inter-telomeric copying occurs, consistent with a mechanism in which single-stranded DNA at one telomere terminus invades another telomere and uses it as a copy template resulting in net increase in telomeric sequence. It is possible that t-loops, linear and/or circular extrachromosomal telomeric DNA, and the proteins found in APBs, may be involved in the mechanism. ALT and telomerase activity can co-exist within cultured cells, and within tumors. The existence of ALT adds some complexity to proposed uses of telomere-related parameters in cancer diagnosis and prognosis, and poses challenges for the design of anticancer therapeutics designed to inhibit telomere maintenance.

Authors+Show Affiliations

Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, Sydney 2145, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11850785

Citation

Henson, Jeremy D., et al. "Alternative Lengthening of Telomeres in Mammalian Cells." Oncogene, vol. 21, no. 4, 2002, pp. 598-610.
Henson JD, Neumann AA, Yeager TR, et al. Alternative lengthening of telomeres in mammalian cells. Oncogene. 2002;21(4):598-610.
Henson, J. D., Neumann, A. A., Yeager, T. R., & Reddel, R. R. (2002). Alternative lengthening of telomeres in mammalian cells. Oncogene, 21(4), 598-610.
Henson JD, et al. Alternative Lengthening of Telomeres in Mammalian Cells. Oncogene. 2002 Jan 21;21(4):598-610. PubMed PMID: 11850785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alternative lengthening of telomeres in mammalian cells. AU - Henson,Jeremy D, AU - Neumann,Axel A, AU - Yeager,Thomas R, AU - Reddel,Roger R, PY - 2002/2/19/pubmed PY - 2002/3/9/medline PY - 2002/2/19/entrez SP - 598 EP - 610 JF - Oncogene JO - Oncogene VL - 21 IS - 4 N2 - Some immortalized mammalian cell lines and tumors maintain or increase the overall length of their telomeres in the absence of telomerase activity by one or more mechanisms referred to as alternative lengthening of telomeres (ALT). Characteristics of human ALT cells include great heterogeneity of telomere size (ranging from undetectable to abnormally long) within individual cells, and ALT-associated PML bodies (APBs) that contain extrachromosomal telomeric DNA, telomere-specific binding proteins, and proteins involved in DNA recombination and replication. Activation of ALT during immortalization involves recessive mutations in genes that are as yet unidentified. Repressors of ALT activity are present in normal cells and some telomerase-positive cells. Telomere length dynamics in ALT cells suggest a recombinational mechanism. Inter-telomeric copying occurs, consistent with a mechanism in which single-stranded DNA at one telomere terminus invades another telomere and uses it as a copy template resulting in net increase in telomeric sequence. It is possible that t-loops, linear and/or circular extrachromosomal telomeric DNA, and the proteins found in APBs, may be involved in the mechanism. ALT and telomerase activity can co-exist within cultured cells, and within tumors. The existence of ALT adds some complexity to proposed uses of telomere-related parameters in cancer diagnosis and prognosis, and poses challenges for the design of anticancer therapeutics designed to inhibit telomere maintenance. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11850785/Alternative_lengthening_of_telomeres_in_mammalian_cells_ L2 - http://dx.doi.org/10.1038/sj.onc.1205058 DB - PRIME DP - Unbound Medicine ER -