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Nucleic Acids Research Advance Access originally published online on January 23, 2007
Nucleic Acids Research 2007 35(3):872-880; doi:10.1093/nar/gkl1100
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Nucleic Acids Research, 2007, Vol. 35, No. 3 872-880
© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest

Lucy Glover, Sam Alsford, Caroline Beattie and David Horn*

London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

*To whom correspondence should be addressed. Tel: (020) 7927 2352; Fax: (020) 7636 8739; E-mail: david.horn{at}lshtm.ac.uk

Eukaryotic chromosomes are capped with telomeres which allow complete chromosome replication and prevent the ends from being recognized by the repair machinery. The African trypanosome, Trypanosoma brucei, is a protozoan parasite where antigenic variation requires reversible silencing of a repository of telomere-adjacent variant surface glycoprotein (VSG) genes. We have investigated the role of the telomere adjacent to a repressed VSG. In cells lacking telomerase, the rate of telomere-repeat loss appeared to be inversely proportional to telomere length. We therefore constructed strains in which a single telomere could be immediately removed by conditional I-SceI meganuclease cleavage. Following telomere deletion, cells maintain and segregate the damaged chromosome without repairing it. These cells continue to proliferate at the normal rate but progressively lose terminal DNA at the broken end. Although sirtuin-dependent repression is lost along with the telomere, VSG-silencing is preserved. The results provide direct evidence for telomere-dependent repression but suggest a telomere-independent mode of VSG-silencing. They also indicate the absence of a telomere-loss checkpoint in T. brucei.


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L. Glover, R. McCulloch, and D. Horn
Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes
Nucleic Acids Res., May 1, 2008; 36(8): 2608 - 2618.
[Abstract] [Full Text] [PDF]


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