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Human Molecular Genetics Advance Access published online on January 18, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddi486
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received November 14, 2005
Revised January 13, 2006
Accepted January 13, 2006

Article

Structural stability and chromosome-specific telomere length is governed by cis-acting determinants in humans

Bethan Britt-Compton 1, Jan Rowson 1, Matthew Locke 2, Ian Mackenzie 3, David Kipling 1, and Duncan M. Baird 1 *

1 Department of Pathology, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
2 Department of Adult Dental Health, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
3 Institute for Cell and Molecular Science, Queen Mary University of London, 2 Newark Street, Whitechapel, London E1 2AT, UK

* To whom correspondence should be addressed.
Duncan M. Baird, E-mail: bairddm{at}cardiff.ac.uk


  Abstract

Single telomere length analysis (STELA) of the XpYp telomere has revealed extensive allelic variation and ultra-short telomeres in senescent cells. Superimposed on end-replication losses are additional mutational events that result in large-scale changes in telomere length. In order to establish if the dynamics of the XpYp telomere are typical of human telomeres, here we describe an analysis using STELA of the telomeres of 2p, 11q, 12q, 17p and XpYp. The dynamics of telomere loss (erosion rates and stochastic length changes) was conserved between 2p, 11q, 12q and XpYp within the same cell strains and was dependent on the replicative kinetics of the cells in culture. However of the telomeres analysed, the telomere of 17p was more stable with a striking paucity of large-scale length changes, it exhibited the shortest recorded allelic distribution (300bp) in senescent cells and displayed a general, but not absolute, trend towards being the shortest telomere. Ectopic over-expression of hTERT homogenised both allelic and chromosome-specific telomeric distributions. However, telomerase expressing cancer cells displayed both allelic variation and chromosome specific telomere length, with 17p displaying the shortest allelic telomere length. Whilst other telomeres in the genome may share the properties of 17p, these data suggest that physiological levels of telomerase allow differential telomere length regulation and indicate the presence of cis-acting factors that govern both telomeric stability and chromosome-specific telomere length in the presence of telomerase.


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