Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes

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

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages21269-21277
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number24
DOIs
Publication statusPublished - 14 Jun 2002
Externally publishedYes

Fingerprint

Trypanosomiasis
Membrane Glycoproteins
Telomere
Genes
Maintenance
Genetic Recombination
DNA
Chemical activation
Telomere Homeostasis
Tsetse Flies
Telomere Shortening
Immune Evasion
Antigenic Variation
Double-Stranded DNA Breaks
Gene Silencing
Pathogens
Chromosomes
Repair
Association reactions
Proteins

Cite this

Conway, Colin ; McCulloch, Richard ; Ginger, Michael L. ; Robinson, Nicholas P. ; Browitt, Alison ; David Barry, J. / Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 24. pp. 21269-21277.
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Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes. / Conway, Colin; McCulloch, Richard; Ginger, Michael L.; Robinson, Nicholas P.; Browitt, Alison; David Barry, J.

In: Journal of Biological Chemistry, Vol. 277, No. 24, 14.06.2002, p. 21269-21277.

Research output: Contribution to journalArticle

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