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J. Biol. Chem., Vol. 277, Issue 24, 21269-21277, June 14, 2002
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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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AJ307890, AJ311845.
Ku Is Important for Telomere Maintenance, but Not for
Differential Expression of Telomeric VSG Genes, in African
Trypanosomes*
,
*
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.
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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