Mismatch repair regulates homologous recombination, but has little influence on antigenic variation, in Trypanosoma brucei.
Antigenic variation is critical in the life of the African trypanosome, as it allows the parasite to survive in the face of host immunity and enhance its transmission to other hosts. Much of trypanosome antigenic variation uses homologous recombination of variant surface glycoprotein (VSG)-encoding genes into specialized transcription sites, but little is known about the processes that regulate it. Here we describe the effects on VSG switching when two central mismatch repair genes, MSH2 and MLH1, are mutated. We show that disruption of the parasite mismatch repair system causes an increased frequency of homologous recombination, both between perfectly matched DNA molecules and between DNA molecules with divergent sequences. Mismatch repair therefore provides an important regulatory role in homologous recombination in this ancient eukaryote. Despite this, the mismatch repair system has no detectable role in regulating antigenic variation, meaning that VSG switching is either immune to mismatch selection or that mismatch repair acts in a subtle manner, undetectable by current assays.
Bell
Joanna S
JS
Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College, 56 Dumbarton Road, Glasgow G11 6NU, Scotland, United Kingdom.
McCulloch
Richard
R
D000818:Animals; D000940:Antigenic Variation; D000941:Antigens / Q000737:chemistry; D020137:Base Pair Mismatch; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005822:Genetic Vectors; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D011995:Recombination, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism
D000941:Antigens; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C435509:MSH2 protein, Trypanosoma cruzi; D051718:MutS Homolog 2 Protein