title: Identification of Trypanosoma brucei RMI1/BLAP75 homologue and its roles in antigenic variation.
abstract: At any time, each cell of the protozoan parasite Trypanosoma brucei expresses a single species of its major antigenic protein, the variant surface glycoprotein (VSG), from a repertoire of >2,000 VSG genes and pseudogenes. The potential to express different VSGs by transcription and recombination allows the parasite to escape the antibody-mediated host immune response, a mechanism known as antigenic variation. The active VSG is transcribed from a sub-telomeric polycistronic unit called the expression site (ES), whose promoter is 40-60 kb upstream of the VSG. While the mechanisms that initiate recombination remain unclear, the resolution phase of these reactions results in the recombinational replacement of the expressed VSG with a donor from one of three distinct chromosomal locations; sub-telomeric loci on the 11 essential chromosomes, on minichromosomes, or at telomere-distal loci. Depending on the type of recombinational replacement (single or double crossover, duplicative gene conversion, etc), several DNA-repair pathways have been thought to play a role. Here we show that VSG recombination relies on at least two distinct DNA-repair pathways, one of which requires RMI1-TOPO3α to suppress recombination and one that is dependent on RAD51 and RMI1. These genetic interactions suggest that both RAD51-dependent and RAD51-independent recombination pathways operate in antigenic switching and that trypanosomes differentially utilize recombination factors for VSG switching, depending on currently unknown parameters within the ES.
authors: Laboratory of Molecular Parasitology, The Rockefeller University, New York, New York, United States of America.
authors: Hee-Sook
authors: HS
authors: Kim
authors: George A M
authors: GA
authors: Cross
mesh_terms: D000940:Antigenic Variation / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma