Rad51-like genes in Trypanosoma brucei: A potential role in antigenic variation

Proudfoot, Chris (2005) Rad51-like genes in Trypanosoma brucei: A potential role in antigenic variation. PhD thesis, University of Glasgow.

Abstract

African trypanosomes, such as Trypanosoma brucei, are single celled eukaryotic parasites of mammals and are the causative agents of sleeping sickness (trypanosomiasis) in humans and nagana in cattle. To avoid being eliminated by the host's immune response trypanosomes undergo a process termed antigenic variation. This consists of spontaneous, periodic changes in the Variant Surface Glycoprotein (VSG) species that acts as a protective coat on the surface of the parasite. Only one gene has been identified thus far to have a role in VSG switching: RAD51. This encodes the eukaryotic homologue of bacterial RecA and archaebacterial RADA, and is central to the catalysis of homologous recombination. radSl-l- T. brucei cells show increased DNA damage sensitivity, have an impaired recombination and reduced levels of VSG switching. However, recombination and VSG switching do still occur, meaning that backup pathways must exist for both processes. The T. brucei genomic databases were searched with T. brucei RAD51, Saccharomyces cerevisiae Rad51 and Escherichia coli RecA sequences to define genes with the potential to encode strand exchange proteins. Five further RADSl-Vike genes were found in this way, and three were chosen for further analysis. The first was named RAD51-3, which has homology to the S. cerevisiae RAD51 co-factor Rad57, as well as H. sapiens RadSlC, in BLAST searches. The second, named DMCl, encodes a protein that is highly homologous to a meiosis-specific form of RAD51 found in many eukaryotes. Finally, the most distantly related of the RAD51-like genes was examined, this was named RADS 1-5 and was identified by searching the T. brucei genome with E. coli RecA. Genetic and biochemical analyses of homozygous mutants of the three genes identified no role for DMC1 in repair, recombination or VSG switching. In contrast, both RADS 1- 3 and RADS 1-5 were shown to have roles in repair, recombination and to mediate the re-localisation of RADS 1 in following DNA damage. Surprisingly, only RADS 1-3 was shown to have a role in VSG switching.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Genetics, parasitology, immunology.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Supervisor, not known
• Date of Award: 2005
• Depositing User: Enlighten Team
• Unique ID: glathesis:2005-71154
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 May 2019 10:49
• Last Modified: 25 Aug 2021 09:06
• URI: https://theses.gla.ac.uk/id/eprint/71154