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Vol. 13, No. 21, pp. 2875-2888, November 1, 1999
The Wellcome Centre for Molecular Parasitology, The Anderson
College, University of Glasgow, Glasgow G11 6NU, U.K.
Antigenic variation is an immune evasion strategy used by African
trypanosomes, in which the parasites periodically switch the expression
of VSG genes that encode their protective variant surface
glycoprotein coat. Two main routes exist for VSG switching: changing the transcriptional status between an active and an inactive copy of the site of VSG expression, called the bloodstream
VSG expression site, or recombination reactions that move
silent VSGs or VSG copies into the actively transcribed
expression site. Nothing is known about the proteins that control and
catalyze these switching reactions. This study describes the cloning of
a trypanosome gene encoding RAD51, an enzyme involved in DNA break
repair and genetic exchange, and analysis of the role of the enzyme in
antigenic variation. Trypanosomes genetically inactivated in the
RAD51 gene were shown to be viable, and had phenotypes
consistent with lacking functional expression of an enzyme of
homologous recombination. The mutants had an impaired ability to
undergo VSG switching, and it appeared that both
recombinational and transcriptional switching reactions were
down-regulated, indicating that RAD51 either catalyzes or regulates
antigenic variation. Switching events were still detectable, however,
so it appears that trypanosome factors other than RAD51 can also
provide for antigenic variation.
[Key Words: Antigenic variation; trypanosome; recombination; RAD51]
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