Article thumbnail

Identification of Trypanosoma brucei RMI1/BLAP75 Homologue and Its Roles in Antigenic Variation

By Hee-Sook Kim and George A. M. Cross


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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1989). A hyperrecombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase.
  2. (1996). A Rad52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae.
  3. (1999). A tightly regulated inducible expression system for dominant negative approaches in Trypanosoma brucei.
  4. (2006). A vector series for rapid PCR-mediated C-terminal in situ tagging of Trypanosoma brucei genes.
  5. (2009). A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei.
  6. (2002). Antigenic variation in african trypanosomes and malaria.
  7. (2001). Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite. In:
  8. (2007). Binding and activation of DNA topoisomerase III by the Rmi1 subunit.
  9. (2008). BLAP18/ RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome.
  10. (2005). BLAP75, an essential component of Bloom’s syndrome protein complexes that maintain genome integrity.
  11. (2006). BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates.
  12. (2006). Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids.
  13. (2007). Break-induced replication and telomerase-independent telomere maintenance require Pol32.
  14. (2008). Break-induced replication: what is it and what is it for? Cell cycle 7:
  15. (2008). CRE recombinase-based positivenegative selection systems for genetic manipulation in Trypanosoma brucei.
  16. (2003). crossovers during double-strand break repair in yeast.
  17. (2010). Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex.
  18. (2010). DNA end resection by Dna2-Sgs1-RPA and its stimulation by
  19. (2006). DNA metabolism and genetic diversity in Trypanosomes.
  20. (1996). Double-strand break repair in the absence of rad51 in yeast: a possible role for break-induced DNA replication.
  21. (2007). Evidence that a RecQ helicase slows senescence by resolving recombining telomeres.
  22. (2010). Extensive DNA end processing by exo1 and sgs1 inhibits break-induced replication.
  23. (1998). Frequent loss of the active site during variant surface glycoprotein expression site switching in vitro in Trypanosoma brucei.
  24. (2006). Function of recQ family helicase in genome stability.
  25. (2008). Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing.
  26. (2004). Gene switching and the stability of odorant receptor gene choice.
  27. (2006). Gene transcription in trypanosomes. Mol Biochem Parasitol 146: 135–141. RMI1 Is Required for T. brucei Antigenic Variation PLoS
  28. (2005). Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium faiciparum.
  29. (2007). Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex.
  30. (2009). Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication.
  31. (2008). Mechanism and regulation of class switch recombination. Annual review of immunology 26:
  32. (2006). Mechanism of homologous recombination: mediators and helicases take on regulatory functions.
  33. (2002). Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae.
  34. (2002). Odorant receptor gene regulation: implications from genomic organization.
  35. (1999). RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase.
  36. (2005). Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase.
  37. (1986). Rapid change of the repertoire of variant surface glycoprotein genes in trypanosomes by gene duplication and deletion.
  38. (2008). RecQ helicases: guardian angels of the DNA replication fork.
  39. (2005). Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations.
  40. (2008). RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability.
  41. (2005). RMI1/ NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex.
  42. (2004). Selective gene expression in multigene families from yeast to mammals. Sci STKE
  43. (2009). Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair.
  44. (1996). SGS1, a homologue of the Bloom’s and Werner’s syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae.
  45. (2010). Structure and cellular roles of the RMI core complex from the bloom syndrome dissolvasome.
  46. (2000). Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rifinhibited recombinational process.
  47. (1996). Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei.
  48. (2008). Telomeric expression sites are highly conserved in Trypanosoma brucei.
  49. (1985). Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes.
  50. (2007). Template switching during breakinduced replication.
  51. (2003). The Bloom’s syndrome helicase suppresses crossing over during homologous recombination.
  52. (2005). The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes.
  53. (1999). The DNA helicase activity of BLM is necessary for the correction of the genomic instability of bloom syndrome cells.
  54. (2007). The RecQ helicase-topoisomerase III-Rmi1 complex: a DNA structure-specific ‘dissolvasome’?
  55. (1994). The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase.
  56. (2006). Top3 processes recombination intermediates and modulates checkpoint activity after DNA damage.
  57. (2010). TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei.
  58. (2008). Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana.
  59. (2002). Two pathways of homologous recombination in Trypanosoma brucei.
  60. (2005). VSG switching in Trypanosoma brucei: antigenic variation analysed using RNAi in the absence of immune selection.
  61. (2005). Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex.