Putative TTAGGG repeat-binding factor
(TRF) homologues were identified in the genomes of Trypanosoma
brucei, Trypanosoma cruzi and Leishmania major. They have significant
sequence similarity to higher eukaryotic TRFs in their C-terminal
DNA-binding myb domains, but only weak similarity in their N-terminal
domains. T. brucei TRF is essential and was shown to bind to duplex
TTAGGG repeats. RNAi-mediated knock-down of tbTRF arrested
bloodstream cells at G2/M and procyclic cells partly at S phase.
Functionally, tbTRF resembles mammalian TRF2 more than TRF1, as
knock-down diminished telomere single-stranded G-overhang signals.
This suggests that tbTRF, like vertebrate TRF2, is essential for
telomere end protection, and supports the hypothesis that TRF rather
than Rap1 is the more ancient DNA-binding component of the telomere
protein complex. Identification of the first T. brucei telomere DNA
binding protein and characterization of its function provides a new
route to explore the roles of telomeres in pathogenesis of this
organism. This work also establishes T. brucei as an attractive model
for telomere biology.