A novel telomere structure in a human alternative lengthening of telomeres cell line

Robert A Marciniak, David Cavazos, Richard Montellano, Qijun Chen, Leonard Guarente, F. Brad Johnson

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies. In Saccharomyces cerevisiae, survivors of telomerase inactivation also use recombination to maintain telomeres. There are two types of survivors, which differ in telomere structure. The first possesses telomere repeats and the Y′ subtelomeric element amplified together as a tandem array at chromosome termini (type I), and the other possesses amplification of telomeric repeats alone (type II), similar to previously described human ALT cells. Here, we describe the first human ALT cell line having "tandem array" telomeres with a structure similar to that of type I yeast survivors. The chromosome termini consist of a repeat unit containing ∼2.5 kb of SV40 DNA and a variable amount of TTAGGG sequence repeated in tandem an average of 10 to 20 times. Similar to previously described ALT cells, they show evidence of telomere recombination, but unlike standard ALT cells, they lack ALT-associated promyelocytic leukemia bodies and their telomeres are transcribed. These findings have implications for the pathogenesis and diagnosis of cancer.

Original languageEnglish (US)
Pages (from-to)2730-2737
Number of pages8
JournalCancer Research
Volume65
Issue number7
DOIs
StatePublished - Apr 1 2005

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Telomere Homeostasis
Telomere
Cell Line
Genetic Recombination
Telomerase
Leukemia
Chromosomes
Neoplasms
Saccharomyces cerevisiae
Yeasts

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A novel telomere structure in a human alternative lengthening of telomeres cell line. / Marciniak, Robert A; Cavazos, David; Montellano, Richard; Chen, Qijun; Guarente, Leonard; Johnson, F. Brad.

In: Cancer Research, Vol. 65, No. 7, 01.04.2005, p. 2730-2737.

Research output: Contribution to journalArticle

Marciniak, RA, Cavazos, D, Montellano, R, Chen, Q, Guarente, L & Johnson, FB 2005, 'A novel telomere structure in a human alternative lengthening of telomeres cell line', Cancer Research, vol. 65, no. 7, pp. 2730-2737. https://doi.org/10.1158/0008-5472.CAN-04-2888
Marciniak, Robert A ; Cavazos, David ; Montellano, Richard ; Chen, Qijun ; Guarente, Leonard ; Johnson, F. Brad. / A novel telomere structure in a human alternative lengthening of telomeres cell line. In: Cancer Research. 2005 ; Vol. 65, No. 7. pp. 2730-2737.
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