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Originally published In Press as doi:10.1074/jbc.M200550200 on March 27, 2002

J. Biol. Chem., Vol. 277, Issue 24, 21269-21277, June 14, 2002
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Ku Is Important for Telomere Maintenance, but Not for Differential Expression of Telomeric VSG Genes, in African Trypanosomes*

Colin Conway, Richard McCullochDagger , Michael L. Ginger§, Nicholas P. Robinson, Alison Browitt, and J. David Barry

From the Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow, G11 6NU, Scotland, United Kingdom

Trypanosome antigenic variation, involving differential expression of variant surface glycoprotein (VSG) genes, has a strong association with telomeres and with DNA recombination. All expressed VSGs are telomeric, and differential activation involves recombination into the telomeric environment or silencing/activation of subtelomeric promoters. A number of pathogen contingency gene systems associated with immune evasion involve telomeric loci, which has prompted speculation that chromosome ends provide conditions conducive for the operation of rapid gene switching mechanisms. Ku is a protein associated with eukaryotic telomeres that is directly involved in DNA recombination and in gene silencing. We have tested the hypothesis that Ku in trypanosomes is centrally involved in differential VSG expression. We show, via the generation of null mutants, that trypanosome Ku is closely involved in telomere length maintenance, more so for a transcriptionally active than an inactive telomere, but exhibits no detectable influence on DNA double strand break repair. The absence of Ku and the consequent great shortening of telomeres had no detectable influence either on the rate of VSG switching or on the silencing of the telomeric promoters of the VSG subset that is expressed in the tsetse fly.


* This work was supported by the Wellcome Trust and the Royal Society.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ307890, AJ311845.

Dagger A Royal Society University Research Fellow.

§ Present address: School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK.

A Wellcome Trust Principal Research Fellow. To whom correspondence should be addressed. Tel.: 0044141-330-4875; Fax: 0044141-330-5422; E-mail: j.d.barry@bio.gla.ac.uk.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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